index [catalogimages.wiley.com]anti-apoptosis, ne-kb family and, 762–763.see also apoptosis...

All-trans retinoic acid (ATRA), 676Alsterpaullone, 683–684ALV-induced chicken lymphomas, 579, 580–581Alzheimer’s disease, 691Amino acids, Ras GTPase activity and, 131–132Amino acid starvation, 412Amino acid transport, 728AML-ETO translocation fusion protein, 24. See

also Acute myeloblastic leukemia (AML)Amphibian life cycles, 370–372Amphibian metamorphosis, 376–377Anaphase, 115, 203, 210–213Anaphase B, 203Anaphase movements, 212Anaphase-promoting complex (APC), 120, 121,

124, 170Anaphase-promoting complex/cyclosome

(APC/C), 50, 211Anaplasia, 745Anchorage dependence, 355Androgen receptor (AR), 168, 169, 174, 738–739Androgen-sensitive prostate epithelial (LNCaP)

cells, 168, 169Aneuploidy, 124Angioblastomas, 352Angiogenesis

bioassays to study, 334blood supply and, 333–367negative regulators of, 340–341pathologic, 343positive regulators of, 334–335retinoblastoma family and, 621–622tumor, 333–353

Angiogenesis inhibitors, 334, 335–338, 336clinical use of, 347–348, 351–353current and future directions of, 353direct and indirect, 345–347

Angiogenic phenotype, oncogenes and, 344–345Angiogenic proteins, 335, 352“Angiogenic switch” model, 339Angiopoietin, expression of, 356–357

INDEX

773

Abelson murine leukemia virus (A-MuLV),575–576

Acetylatable lysines, mutation of, 267Acetylated histones, 108Acetylation, p53 function and, 649ACF (ATP-utilizing chromatin assembly and

remodeling factor) complex, 281, 282Active transport systems, 724Activity-driven assembly, of regulatory foci, 25–26Acute lymphoblastic leukemias, 273. See also

ALL entriesAcute myeloblastic leukemia (AML), 557, 690,

736. See also AML-ETO translocation fusionprotein; Runx/Cbfa/AML transcriptionfactor

therapy for, 674Acute myelogenous leukemia, 62Acute myeloid leukemia, 270, 688–689Acute promyelocytic leukemia (APL; PML), 272,

738, 747. See also PML entriesAcute transforming viruses, 572Adducin, 682Adenovirus vectors, 656–657AdoMetDC, 409Adrenal cortical tumors (ACT), 655Adversity, adaptation to, 372Aggressive tumors, 350Aging

accelerated rates of, 459cancer incidence and, 747–751

Agno protein, 468–469Agonescence, 748AKT8 retrovirus, 581Akt activity, 596Akt protein family, 508, 510, 650, 769, 770. See

also Phosphatidylinolitol-3 kinase/Aktpathway

ALL-1 regulatory protein, 28, 49Allatostatins, JH production and, 379ALL foci, 20. See also Acute lymphoblastic

leukemias

Cell Cycle and Growth Control: Biomolecular Regulation and Cancer, SecondEdition, Edited by Gary S. Stein and Arthur B. PardeeISBN 0-471-25071-6 Copyright © 2004 by John Wiley & Sons, Inc.

index.qxd 3/24/04 2:57 PM Page 773

774 INDEX

Angiopoietin-1, 355Animal models, nonhomologous end-joining gene

mutations in, 548–551Ankyrin repeat, 241Antephase, 215

MAPKs and, 217Antephase-to-mitosis transition, control of, 216“Anti-angiogenesis,” 333Antiangiogenic chemotherapy, 348–349

versus antivascular therapy, 350Antiangiogenic drugs, 351Anti-apoptosis, NE-kB family and, 762–763. See

also ApoptosisAnticancer drugs, 345–347. See also Drugs;Therapies

mitochondria-targeted, 761Anticancer strategies, 736Antisense RNA, 417, 419Antivascular therapy, versus antiangiogenic

therapy, 350APC (adenomatous polyposis coli) protein, 59APE1 endonuclease, 539–541apg-related genes, 385Apical sensory ganglia (ASG), 375Apoptosis, 9, 10, 64–65, 497–521, 592–595, 715,

751–765. See also Anti-apoptosis; Apoptoticentries; Autophagic programmed cell death;PUMA (p53 upregulated mediator ofapoptosis); Death entries; xR11 anti-apoptotic protein

activation-induced, 142cancer and, 507–513caspases and, 761–762DNA damage and, 769during Drosophila metamorphosis, 383–386E2F-1 and, 756–758endothelial cell, 349Fas/FasL-mediated, 140hallmarks of, 65in Ilyanassa obsoleta, 375major mediators of, 498–505mechanisms of, 498, 759–765mitochondria and, 759–761normal physiology and, 507oncogenes and, 592p27 and, 247p53 and, 753–755regulators of, 513restoring to tumor cells, 758–759retinoblastoma family and, 618–619TRAIL-induced, 689

Apoptosis gene promoters, 384–386Apoptosis signaling, 497–521

pathways for, 505–507“Apoptosome,” 505Apoptotic pathways

defects in, 497oncogene subversion of, 593–595p53 and, 642–646

Apoptotic treatment, 754–755APO/TRAIL interactions, 503apterous gene, 375archipelago (ago) mutant, 387Architectural assembly, of regulatory foci, 25–26Architectural control, of DNA synthesis, 36–39Architectural modifications, through apoptosis, 65Arf expression, p53 and, 649ARF promoter, 757ARF proteins, nucleolar, 31. See also p14ARF

protein; p19Arf proteinArg to His substitution, 654, 655ARG (Abl-related gene), 686ARS elements, 161, 163Artemia salina, 372Artemis factor, 546Asparaginase, 671Asters, 202, 206

separation of, 204Astral microtubule density, 218Astral microtubules, 204, 206, 208Asymmetric cell division, 61Ataxia telangiectasia protein (ATM), 9, 122–123,

478, 765. See also ATM entriesDSB detection by, 52

AT-like disorder (AT-LD), 548ATM/ATR serine/threonine kinases, 216ATM/ATR signal transduction, 58ATM (ataxia-telangiectasia mutated) mutations,

101ATPases, 47

SNF2 family, 277ATPase subunits, 276ATP (adenosine triphosphate) binding, 678

site for, 242ATP-dependent chromatin remodeling, 276ATP-dependent regulators, of chromatin

structure, 47–48ATP depletion, 751ATP production, 761ATR/ATRIP signaling, 52ATR protein, 122–123, 478, 765A-type HATs, 267–268AUG codons, 419Aurora kinase family, 275Autonomously replicating sequence (ARS)

elements, 158Autophagic programmed cell death, 383–384. See

also Apoptosisgenes induced prior to, 385–386

Avascular tumors, 340Avastin, 352–353Avian myeloblastosis virus (AMV), 577, 579Avian sarcoma virus 16 (ASV16), 591Away-from-the pole (AP) motion, 208

Baehrecke, Eric H., 369Bai, Uma, 149


Baker, Stacey J., 571Barrack, Evelyn R., 149BASC complex, 58Base excision repair, 538–543Basement membrane (BM), 297Basement membrane collagens, 300

diseases of, 301Bax/Bak oligomerization, 501Bax death family, 500Bax gene, 643–644Bax proteins, 10B-cell chronic lymphocytic leukemia, 681B-cell lymphoma 2 (Bcl-2) family, 499–502. See

also Bcl-2 protein familyB-cell lymphomas, 273, 274, 576B-cell proliferation, 140–143bcl-2 (B-cell leukemia/lymphoma-2) gene, 592Bcl-2 protein family, 10, 345, 507, 510, 512, 759.

See also B-cell lymphoma 2 (Bcl-2) familyBcl-XL proteins, 512, 592bcr-abl gene, 585, 675, 676, 686BCR-ABL protein, 585BCR-ABL translocation

morphological diagnosis and, 685–686B cyclins, synthesis of, 424. See also Cyclin BBd-2 family, 754Beckwith-Wiedemann syndrome, 248Benvenuti, Silvia, 467bFTZ-F1 gene, 383b-globin gene, 160–161

timing of replication in locus of, 161–162bFGF expression, 352bFGF-producing tumors, 347BH3-only proteins, 500, 501, 512BH domains, 592Bioassays, for angiogenesis study, 334Biochemical endpoint, 687Biochemistry, of cycle phases, 6–8Biological control, nuclear organization and, 16–19Biological regulation, challenges and

opportunities related to, 65–66“Bioriented” chromosome, 209Biotinylated-dUMP, 176, 177Bissell, Mina J., 297Bladder cancer, 427–428BLIMP-1 gene, 275BLM helicase, 558Blood supply, angiogenesis and, 333–367Blood vessels, normal, 353–357Bloom’s syndrome, 558, 747BM28 protein, 167Bortezomib, 688Braastad, Corey D., 15BRCA1 gene, mutations in, 555–556BRCA1 tumor-suppressor, 59, 60, 279, 712

cancer and, 554BRCA2 function, 712

cancer and, 556

INDEX 775

BRCA2 gene, 551BRCA2 protein, 553BRCA complex, 58BRCA foci, 21BR-C gene, 382Breast cancer, 60, 275, 427, 459–460, 691. See also

BRCA entries; Breast tumorsBRCA2 and, 556eIF4E elevation and, 429FGF-2 isoforms and, 419metastasis of, 739p27 and, 251replication complexes associated with, 174VEGF and, 334

Breast Cancer Information Core, 555Breast cancer susceptibility genes, 57

product of, 279Breast tumors, 709BRG1 subunit, 47–48, 278–280BRM protein, 278–280B-type HATs, 267B-type lamins, 177Bub (budding uninhibited in benzimidazole)

proteins, 50, 124Budding yeast. See also Saccharomyces cerevisiae

cell cycle of, 98G1ÆS progression in, 413–416

Burkitt’s lymphoma, 408, 580–581, 585Butyrolactone, 684

Ca++ (calcium ion), mitochondrial storage of, 760c-abl oncogene, 575–576, 585Ca++/CaM, role in DNA synthesis, 175Cadherin-catenin complexes, 726Cadherin levels, 729C-akt gene, 581Calcyculin, 405Calmodulin (CaM), 151. See also CaM-BP68

proteinCalpain, 314CaM-BP68 protein, 175, 177cAMP (cyclic AMP), 141Cancer, 707–771. See also Breast cancer; Cancer

cells; Cancer susceptibility; Carcinogenesis;Cervical cancer; Colon cancer; Leukemias;Malignancies; Melanomas; Metastasis;Oncogenes; Ovarian cancers; Pancreaticcancers; Tumor entries

aging and, 747–751apoptosis and, 64, 507–510BRCA1/2 function and, 554–556cell cycle and, 741–745cell cycle inhibitors and, 250–252centrosome amplification and, 222checkpoint allele loss and, 49checkpoint control and, 101–103chromatin remodeling and, 265–295compartmentalization in, 720–721


776 INDEX

death receptor-induced apoptosis defects and,510

DNA methylation and histone acetylation in,717–719

dysregulation and, 714–716extracellular regulation of, 723–724extracellular structures and, 725–727familial syndromes of, 101future developments related to, 769–771gene expression in, 713–714growth factors and, 727–730growth termination in, 745–751HAT activity misregulation and, 269–270hereditary, 711–712histone acetyltransferase overexpression and,

270–271hMLH1/2 genes and, 533homologous recombination genes and,

556–558initiation factors for, 428intracell signaling in, 730–741intrinsic pathway dysregulation and, 509–510kinase cascades in, 734–736levels of regulation in, 716–721mutation and, 114, 709–714MYST family and, 268–269naturally occurring, 427–428postmitochondrial death process inhibition

and, 510post-transcriptional regulations in, 719–720pro-survival signaling and, 508–509proteasomes in, 720protein synthesis deregulation and, 425–430Ras and, 731–734retinoblastoma family deregulation in, 622–625ribosomal biogenesis levels of, 31stressed cells and, 765–769

Cancer cellscontrols in, 716–717defenses against apoptosis, 754differentiation and arrest of proliferation in,

745–747proliferation of, 716–717, 741–742quiescence versus proliferation in, 721–730versus normal cells, 707–709

Cancer genetics, advances in, 497–498Cancer prognosis, telomere length and, 455–456Cancer research, 708Cancer screening, 429Cancer susceptibility

base excision repair and, 542–543homologous recombination and, 554mismatch repair and, 532nonhomologous end-joining and, 548nucleotide excision repair and, 537–538

Cancer therapy, 708. See also Chemotherapyapoptosis and, 510–513

cell cycle and, 670–690protein synthesis factors and, 429–430

Cancer viruses, 712–713Canine thyroid tumors, 333Cap-dependent translation, 411–412, 422Capillary blood vessels, 353–354Carbohydrates, cell-surface soybean agglutinin

(SBA) binding, 726Carboxy-terminus (C-terminus) region, 609Carcinogenesis, 711. See also Cancer entries

Myc and, 737–738telomere loss and, 459telomere malfunction and, 454–455

Carcinogens. See Chemical carcinogensCarneiro, Carmen, 237Caspases, 10, 506

apoptosis and, 498–499, 761–762regulation of, 499

CBP gene, 270CBP protein family, 269, 270, 482–483CD28, 140, 141

role of, 142CD44 adhesion molecule, 426CD95-L, 510CD437, 768Cdc2/cdc28 kinase, 152cdc2 gene, 98, 116Cdc6

MCM protein loading and, 167in Xenopus laevis, 166

Cdc6/Cdc18, 164–165binding of, 169, 171origin loading factors of, 164

Cdc7 kinase activity, 171Cdcl8, overexpression of, 172Cdc20 protein, 50, 120, 124

inactivation of, 221Cdc25A phosphatase, 53Cdc25B phosphatase, 206Cdc25C phosphatase, 122, 216, 217

inactivation of, 123Cdc25 family, 117, 205, 766CDC33 gene, 414cdc33-1 mutant, 414, 415Cdc45 protein, 171

homologues of, 168pre-RC activation and, 169

Cdc (cell division cycle) mutants, 97Cdk1 (cyclin-dependent kinase 1), 8, 116, 681

phosphorylation of, 116–117Cdk1 activity, inhibition of, 123Cdk1/cyclin B1, 206Cdk1/cyclin B2 complex, 205Cdk1-cyclin B activation, 217Cdk2, 677, 736CDK2 activity, inhibition of, 53CDK2 complex, 241–242


CDK4 protein, 238–239, 241CDK6 protein, 238–239, 241Cdk-activating kinase (CAK), 7, 117CDK activities, 111

during the cell cycle, 111level of, 99

CDK enzymes, 98–99as cell cycle regulators, 99–100

Cdk inhibition, restoration of, 685Cdk inhibitory proteins (CKIs), 44, 154–155,

677–684, 691, 742. See also Cell cycleinhibitors; Cyclin-dependent kinaseinhibitors (CKIs)

clinical development of, 684–688E2F regulated, 114redundancy or compensatory roles of, 249–250

CDKIs. See Cdk inhibitory proteins (CKIs)CDK-Rb-E2F activation, prevention of, 114CDK-Rb-E2F pathway, 107, 113, 114CDKN2A tumor-suppressor locus, 748Cdt1 origin loading factor, 164–165Cell adhesion-mediated signals, 315Cell cycle, 129, 715. See also Mitosis

“architecturally linked” crosstalk in, 64biochemical parameters of, 15–16biology of, 4–6cancer and, 741–745cancer therapy and, 670–690CDKs as regulators of, 99–100, 111cell withdrawal from, 237decisions concerning, 252–253“division of labor” in, 37drug resistance and, 688–690dynamic redistribution during, 44–45entrance into, 137–143genes related to, 690–691growth control and, 669–703mRNA-specific translational control and,

407–413nuclear envelope changes during, 62–64proliferative regulation of, 9purpose of, 201regulatory mechanisms of, 10–12role of nuclear membrane in, 179signal transduction and, 130studying, 97–99translational control and, 397–448

Cell cycle arrest, 54, 271, 639–640transient, 100

Cell cycle checkpoint controls, differences in,757–758

Cell cycle checkpoints, 49–50oncogene subversion of, 595–598

Cell cycle components, targeting in nonmalignantdisorders, 691

Cell cycle control, 150. See also Cell cycleregulation

INDEX 777

biochemical changes in, 16p53 and, 639–640proliferation/differentiation, 60–62regulatory mechanisms of, 11–12temporal-spatial parameters of, 30–65

Cell cycle deregulation, cancer and, 425–430Cell cycle inhibitors, 237–264. See also Cdk

inhibitory proteins (CKIs); Cyclin-dependentkinase inhibitors (CKIs)

cancer and, 250–252families of, 241–242

Cell cycle parameters, diagnostic and prognosticuse of, 690–691

Cell cycle phases, 95–96Cell cycle progression, 238–255

E2F transcriptional target role in, 109–114effects of cell-ECM interactions on,

310–319integrin signaling and, 319limiting, 113multilayered regulation of, 110proteolysis in, 155–156regulators affecting, 152–156signaling pathways in, 150–152

Cell cycle regulation, 96. See also Cell cyclecontrol

compounds that target, 670–671by cyclins and cyclin-dependent kinases,

152–154integrin-mediated signaling and, 316–319

Cell cycle regulatory cascades, 95–128Cell cycle regulatory proteins, 48–49, 242Cell cycle target-specific therapies, 675–684Cell cycle transition, retinoblastoma family,

610–612Cell cycle traverse

direct inhibitors of, 677–684indirect inhibitors of, 687–688

Cell death. See Apoptosis; Autophagicprogrammed cell death; PUMA (p53upregulated mediator of apoptosis)

Cell Death and Differentiation, 636Cell division (cytokinesis), 6. See also Mitosis;

Mitotic entriesasymmetric, 61proteasomes and, 45

Cell-ECM interactions, effects on cell cycleprogression, 310–319

Cell extrinsic pathway triggers, 506Cell fusion experiments, 161, 149Cell growth/division. See also Cell proliferation

arrest of, 271coordination of, 95–96large T antigen and, 482mammalian, 417mTOR pathway blocking and, 420–421

Cell intrinsic pathway, 505–506


778 INDEX

Cell machinery, external conditions affecting,723

Cell proliferation, 397, 715. See also Cell growth;Proliferation

differentiation and arrest of, 745–747effects of extracellular matrix on, 306–310genetic regulation of, 386–387insulin-stimulated, 412integrins and, 136, 311–319regulation of, 297–332

Cell remodeling, development growth regulationduring, 386

Cell replication, 114Cells. See also Cell cycle; Cell growth; Cell

proliferation; Cellular entries; Cultured cells;Nuclear entries

alternative pathways of, 3exit from mitosis, 119–121fates of, 3–13immortalization of, 750malignant transformation of, 425molecular and information transfer in, 4

Cell senescence, cancer and, 747–751Cell separation (cytokinesis), 8Cell-specific changes, ecdysone and, 381Cell structure, at the G1ÆS phase transition,

31–35Cell surface adhesion molecules (CAMs), 725Cellular age, intrinsic mechanism for recording,

452–453Cellular compartments, 720–721Cellular events, 715–716Cellular-IRES-containing mRNAs, 411Cellular IRESes, 410, 411Cellular morphology, modifications in, 16Cellular oncogenes, 571–573Cellular regulatory machinery, dynamic assembly

and activities of, 23–26Cellular senescence, p53 and, 640–642Centrioles, 214Centrosomal microtubules, 206Centrosome amplification, 221–223Centrosome cycle, 50Centrosomes, extra, 221–222C/EBPS family, 620Cervical cancer, 712CG8304 gene, 385cGMP (cyclic guanosine monophosphate), 729CGP74514A, 683Chaperone proteins, 481CHD (chromo-helicase-DNA-binding) proteins,

282–283Checkpoint activation, S progression arrest and,

53Checkpoint control

cancer and, 101–103in the metaphase-anaphase transition, 218

Checkpoint cycles, 49–54Checkpoint genes, apoptosis and, 10Checkpoint mechanism, 100–101Checkpoint pathways, 215“Checkpoint rads,” 51Checkpoints, 214–215, 743

depressed, 675as a surveillance mechanism, 100–101

Chemical carcinogens, oncogenes and, 585–587Chemokines, 730Chemotherapeutic agents, 335–336, 342, 708Chemotherapy, 347, 429–430

antiangiogenic, 348–349cytotoxic, 349low-dose, 349

Chfr (checkpoint with FHA and ring finger)gene, 216–217

Chironomus tentaus, ecdysone in, 377–378Chk1/Chk2 kinase, 216chk2 mutants, 101CHOC 400 cell line, 159CHO cells, protein synthesis in, 422Chorian gene, 160CHRAC (chromatin accessibility complex),

281Chromatid disjunction, 211Chromatin. See also Chromatin remodeling

cell cycle-dependent remodeling of, 31licensing factor binding to, 179MCM10 and, 167retinoblastoma family interaction with,

614–616Chromatin arrays, 41Chromatin condensation, 65Chromatin fibers, 266Chromatin-modifying complexes, 615–616Chromatin organization, 40–41Chromatin remodeling, 28, 278

ATP-dependent, 276cancer and, 265–295complexes in, 47–48enzymes in, 265, 554histones and, 45

Chromatin states, open or closed, 108Chromatin structure, 11, 18–19, 265–267

ATP-dependent regulators of, 47–48chemical modification of, 267influences on, 108levels of, 40–43

Chromodomains, 268Chromokinesins, 207Chromonema, 41–42Chromosomal abnormalities, oncogenes and,

584–585Chromosomal changes, 711Chromosomal condensation, 275Chromosomal DNA, replication of, 176


Chromosomal instability, 768–769Chromosomal neighborhoods, 42–43Chromosomal territories, 42–43Chromosomal translocation, 270, 272, 527–528,

586Chromosome attachment, duration of mitosis

and, 218–219Chromosome-based spindle assembly, 207Chromosome condensation, 202, 266

arrested, 215Chromosome cycle, 39–43. See also Cell cycleChromosome disjunction, synchronous, 220Chromosome number, alterations in, 527Chromosome puffing, 382Chromosomes

breakage of, 549–551compartmentalization of, 21–22positioning of, 22recombinogenic, 453

Chromosome segregation, 10, 218genome packaging to accommodate, 39–43

Chromosome territories, 21–22Chronic myelogenous leukemia (CML), 584, 676,

684, 711leukemic cell persistence in, 689–690

Cifuentes, Eugenia, 149CINK4, 682–683Cip1 mutation, 154Cip/Kip cell cycle inhibitor family, 44, 105,

241–242members of, 245–249

cis-acting factors, 408cis-acting signals, 155Clash hypothesis, 715Cleavage apparatus, 213Cleavage failure, 223Clinical trials, design of, 674–675Cln1 cyclin, 414Cln2 cyclin, 413, 414Cln3 cyclin, 414CLN3 gene, eIF4E defect and, 415CLN3 mRNA translation, 415Closed chromatin state, 108cMet receptor, 139CMGC group, 677c-myb oncogene, 577, 579–581c-myc oncogene, 549–551, 577–578, 579, 585. See

also Myc oncogenemRNA of, 408

c-Myc transcription factor, 418, 640, 737activation of, 752

Cockayne syndrome (CS), 538Cohesin complexes, 41, 211Colitis, ulcerative, 455Collagen mutations, 300–301Collagens, 300–301, 308Collagen XVIII, 342–343

INDEX 779

Colon cancer, 428, 455, 683, 686, 713. See alsoColorectal cancers; Hereditary nonpolyposiscolon cancer (HNPCC)

cell lines from, 430, 648Colorectal cancers, 246, 275, 352Combinatorial control, 29COMPARE algorithm, 683Compartmentalization, in cancer, 720–721c-(cell) oncogenes, 574Condensin, 266

complexes, 41Contact inhibition, 137, 355“Continuum model,” 138Convergence pathway, 512–513COOH-terminal serum-sensitive sites, 406Coregulatory factors, 26–27Co-repressor complex, 271Corpus allatum (CA), 378, 379Corticotrophin releasing hormone (CRH), 376Covalent modifications, 11CP-257042, 513CP-31398, 513Cpd 5 drugs, 745CPEB protein, 424CpG hypermethylation, 718c-ras genes, 577CREFT24/AS cells, 426Crisis, 470, 641Crustacea

life cycles of, 370metamorphosis in, 377–378

c-src oncogene, 574–575, 590. See also srconcogene

growth factors and activation of, 590–591CUG codons, 419Cultured cells, cell cycle progression in, 310–319Cycle-dependent kinases, 7Cycle phases, biochemistry and molecular

biology of, 6–8. See also Cell cycle entriesCyclin A, 111, 115, 152–153Cyclin A/Cdk2, 153–154, 156Cyclin A expressor, E2F-dependent upregulation

of, 114Cyclin A-kinase complex, 10Cyclin B, 8, 111, 115. See also B cyclins

synthesis and destruction of, 423Cyclin B1, subcellular localization of, 117Cyclin B/Cdk1, regulation of, 116–118Cyclin B/Cdk1 activity

subcellular localization and, 117targets of, 118–119

Cyclin B/Cdk1 complex, 115Cyclin B degradation, 219, 220Cyclin B levels, 115–116

throughout the cell cycle, 115–116DNA damage and, 122

Cyclin B proteins, 205

index.qxd 3/24/04 2:57 PM 79

780 INDEX

Cyclin B synthesis, 116Cyclin/CDK complexes. See also Cyclin-

dependent kinases (CDKs)G1ÆS transition and, 238–240retinoblastoma family interaction with,

612–613Cyclin/Cdk inhibitors, 154–155, 742. See also

Cyclin-dependent kinases (CDKs)association with DNA-replication enzymes, 157Rb regulation by, 105–106

Cyclin D, complexes with, 239–240. See alsoD-type cyclins

Cyclin D1, 417–418colon cancer and, 428–427overexpression of, 136regulation of, 319

Cyclin D1/cdk4, 622Cyclin D2, 691Cyclin D binding, 318Cyclin D/Cdks, 7Cyclin D-CDK4/6 complexes, 252Cyclin degradation, 120Cyclin-dependent kinase inhibitors (CKIs),

117–118, 154, 169, 242–249, 596. See also Cdkinhibitory proteins (CKIs); Cell cycleinhibitors

degradation of, 155expression and sequential activation of, 153Ink4 family versus, 105negative regulatory function and, 155new roles for, 253–255phosphorylation of, 155–156

Cyclin-dependent kinases (CDKs), 7, 97, 103, 106,115–116, 205, 742. See also CDK entries;Cyclin-CDK complexes; Cyclin/Cdkinhibitors

activation of, 238ATP-competitive inhibitors of, 673as cell cycle regulators, 152–154control of, 240cyclin D and cyclin E dependent, 106–105in DNA synthesis regulation, 156–157expression and sequential activation of, 153Rb proteins and, 105–106, 595role of, 169–172

Cyclin E, 152–153, 240, 613, 690complexes with, 239

Cyclin E binding, 318Cyclin E/Cdk2, 169Cyclin E/CDK2 signaling, 35Cyclin E transcription, Rb and, 615Cyclin-Rbs-E2F pathways, 625Cyclins, 7. See also Mitotic cyclins

as cell cycle regulators, 152–154regulation of, 130

Cyclosome activity, 43–44Cysteine-rich domain (CRD), 132

Cystic fibrosis (CF) gene, 161Cytarabine, 674, 688, 690Cytoarchitecture, 16Cytochrome p450 proteins, 586Cytokinesis, 6, 8, 210Cytoplasmic components, biochemical

modification of, 206Cytoplasmic licensing factor, 179Cytoplasmic microtubule complex, 216Cytoplasmic poly(A), addition of, 412Cytoplasmic polyadenylation, 423–424Cytoplasmic retention signal (CRS), 117, 205Cytotoxic agents, 671–675

cell cycle specific activity of, 672

D1 mRNA, 417, 418D2-CDK4 complexes, 596Damage checkpoints, 767Daughter cells, separation of, 213–214Daunorubicin, 674, 690Dbf4-dependent Cdc7 kinase (DDK), 169, 171Dbf4 protein, 171D-CDK4 complex, 242dE2F genes, 112–113Death-associated protein kinase (DAPk), 385.

See also ApoptosisDeath effectors, p53 and, 504Death-inducing signaling complex (DISC), 503,

506, 507Death receptor (DR), 502–503Death receptor pathways, 506Death receptor-induced apoptosis defects, cancer

and, 510DeGregori, James, 95Deininger, Michael, 669Denhardt, David T., 129Dense fibrillar component (DFC), 30Deoxynucleoside triphosphate (dNTP), 173

compartmentation of, 175Deoxynucleotide metabolism, enzymes of, 173Deoxyribonucleic acid (DNA). See also DNA

entries; Double-strand breaks (DSBs);Heritable DNA; Linker DNA; mtDNA(mitochondrial DNA); rDNA genes

drugs that target, 671duplication of, 4mitotic condensation of, 31nucleosomal, 32re-replication of, 172telomeric, 452

Dermatomyositis, 282Destruction boxes, 120Development, retinoblastoma family and,

617–618. See also “Direct development”Developmental arrest, linkage to intranuclear

trafficking, 25Developmental events, ECM receptors and, 298


Development mechanisms, study system for,380–382

DHFR promoter, deletion in, 161Diacylglycerol (DAG), 141Diagnosis, cell cycle parameters and, 690–691Differentiation

nuclear architecture and, 61–62p27 and, 254retinoblastoma family and, 619–621

Differentiation-inducing agents, 687Dihydrofolate reductase (DHFR) locus, 158, 159Dimerization, 6Diploid cells, nonhomologous end joining in, 55Direct-acting carcinogens, 586Direct angiogenesis inhibitors, 345–347“Direct development,” 370Disease. See also Cancer; Skin disease

ECM component mutations in, 298–299extracellular matrix component mutations in,

299fibrillar collagen, 300–301growth control loss during, 669transcription factor organization and, 62

distal-less gene, 375DNA checkpoint control, 101–103. See also

Deoxyribonucleic acid (DNA)DNA damage, 765–766

cell death and, 769cyclin B levels and, 122response to, 454sensing and signaling, 52–53

DNA damage checkpoints, 9–10, 50, 766–769architectural features of, 51nuclear architecture fidelity at, 52

DNA damage-induced G2 checkpoint, 121–124DNA degradation, Ku binding and, 56DNA-dependent protein kinase (DNA-PK), 546,

766. See also DNA-PK entriesDNA double-strand breaks, 546, 548

nonhomologous end-joining of, 543–551RAG1/RAG2-induced, 549

DNA fibers, long, 157DnaK proteins, 481DNA ligase IV, 547, 548DNA methylation, in cancers, 717–719DNA methyltransferases (DnMT1), 38, 177, 717DNA mismatch, repair mechanism of, 530–532DNA-PK activity, 56DNA-PK complex, 55DNA polymerase-a, 7, 177DNA polymerases, 173, 175DNA precursor (dNTP) synthesis, 180DNA repair, 21, 526–528

architectural organization of, 58defects in, 747via homologous recombination in tetraploid

cells, 56–57

INDEX 781

via nonhomologous end joining in diploid cells,55–56

via single-strand annealing, 57–58steps in, 765

DNA repair cycle, 54–58DNA repair pathways, 528, 765DNA replication, 8, 115

coupling with histone gene expression, 32DNA movement during, 37histone biosynthesis and, 33initiation sites for, 158–159onset of, 155origins of, 157–162protein support for, 36–37rapidity of, 173structural model for, 36

DNA replication control, nuclear context in,176–179

DNA replication enzymes, recruitment of, 171DNA replication sites, enzyme and protein

localization at, 177DNA synthesis, 8, 21

architectural control of, 36–39Cdks in regulation of, 156–157drugs that interfere with, 671factors that mediate, 17

DNA-synthesis-associated enzymes/proteins,cyclin/Cdk-mediated expression of, 156–157

DNA synthesis enzymesfunctional interaction between, 175physical interaction between, 173–175in replication complexes, 172–175

DNA synthesis initiators, at replication origin,162–172. See also trans-acting proteins

DNA viruses, 39dNTP synthesis, 173–174Docking domains, 135Dominant transforming genes, isolation from

human tumors, 582–584Dose, defining, 686–687Double knockout mice, 249–250, 273Double-strand breaks (DSBs), 54

sensing of, 52Downstream events, 7–8Down syndrome, solid tumors and, 342Dpp (decapentaplegic) protein, 374–375DP proteins, 168DRG-1 (tumor suppressor gene 1), 718Drosophila chorian gene, 160Drosophila melanogaster

degradation of cyclin B in, 220developmental stages of, 370ecdysone in, 376–377genetic studies of, 112ISWI-containing complexes in, 281metamorphosis in, 380–387mutations in, 168


782 INDEX

programmed cell death during metamorphosisin, 383–386

salivary gland cell death in, 384wing formation in, 374–375

Drosophila polo, 121Drug administration, 671–674Drug combinations, 770Drug resistance, cell cycle and, 688–690Drugs. See also Chemotherapeutic agents

differentiation-reactivating, 746S-phase specific, 688–689

Drug therapy, for malignant disease, 670. See alsoChemotherapy

DSB repair complexes, 58DSB repair pathways, 54–55D-type cyclins, 105, 152, 238. See also Cyclin D;

Cyclin D1Ductal carcinomas, avascular and invasive, 427Dynamic redistribution, of nuclear proteins,

48–49Dyskeratosis congenita, 459Dysregulation, 714–716Dystroglycan, 306, 309

E1. See Ubiquitin-activating enzyme (E1)E1A oncoprotein, 104, 269–270E2. See Ubiquitin-conjugating enzyme (E2)E2F-1/p73 pathway, 756E2F-1 protein, 7, 168, 743, 744

activity of, 614apoptosis and, 756–758inactivation of, 617mutations of, 757

E2F activity, 241, 609, 741Rb control of, 107–109

E2F-dependent transcription, 107, 113, 114E2F-DP-1 complex, 753E2F/DP heterodimers, 111E2F family, 318. See also E2F transcription

factorsroles of, 112specific functions for, 111–113

E2F inhibition, 105E2F-mediated feedback loops, 113–114E2F-mediated gene repression, 109E2F-mediated transactivation, 271E2F-regulated genes, 108, 110E2F regulation, 59–60E2F transcriptional targets, 110

role in cell cycle progression, 109–114E2F transcription factors, 33, 35, 103, 104, 156,

239–240, 474–475, 476, 611–612, 616E3. See Ubiquitin ligase enzyme (E3)E7 oncoproteins, 608, 609E93 gene, 384Eap1 protein, 416E/Cdk2 activity, 111, 154

E-CDK2 complexes, 44, 239, 252E/Cdk2 protein, 169

activation of, 107Ecdysone-regulated genes, 382, 384Ecdysone-regulated responses, 381–382Ecdysones, 377–378, 380, 381ECM adhesion, effect of, 315ECM components. See also Extracellular matrix

(ECM)homozygous knockouts of, 307as thin monolayer coats, 310–311

ECM-initiated signals, 310ECM-mediated cell cycle control, 318ECM-mediated signals, 311ECM mutations, 308–309ECM proteins, 725–726ECM receptor mutations, 308–309ECM receptors, 298ECM remodeling, 740ECM signaling, 316–318ECM-to-nucleus signaling, 311–314EcR mutants, 382eEF1 elongation factor, 400–401eEF2 enzyme, 401

phosphorylation of, 422Effector caspases, 498–499“Effector” proteins, 101Eg5 protein, phosphorylation of, 118–119EGFP-LRB protein, 63. See also Epidermal

growth factor (EGF)Egr1 gene, 735eIF2B initiation factor, 401–403eIF4E defect, CLN3 gene and, 415eIF4E gene, 414. See also eIF4E initiation

factorectopic overexpression of, 418effect on mammalian cell growth and division

rates, 417manipulation of the expression of, 425–426overexpression of, 419, 420transcription of, 405

eIF4E initiation factor, 403–405, 417–418overexpression of, 425–426protein synthesis and, 404

eIF4E levels, 428, 429eIF4F initiation factor, 422eIF4G gene, manipulation of the expression of,

426eIF4 initiation factors, 399, 408El-Deiry, Wafik S., 497Elongation factors, 400, 401Embryo development, transcriptional activation

of genes during, 161Embryonic lethality, 307End-joining, nonhomologous, 543–551Endocrine control, of metamorphosis, 379–380Endogenous angiogenesis inhibitors, 341


Endogenous nitric oxide synthetase (NOS),375

Endostatin, 336–338, 347anti-angiogenic activity of, 342–343tumors inhibited by, 338

Endostatin administration, continuous, 339Endothelial cells

cloning of, 334proliferation of, 355vascular, 347–348

Enhanced green fluorescent protein (EGFP)fused replication proteins, 38

“Enphores,” 11Entactins, 302–303Enzyme interactions, allosteric nature of, 175Enzymes, 6. See also DNA synthesis enzymes

DNA synthesis, 7–8, 156–157of deoxynucleotide metabolism, 173localization at DNA replication sites, 177

Epidermal growth factor (EGF), 5, 107, 136proliferation activation by, 6

Epidermal growth factor receptor (EGFR), 315,316, 587, 590, 727

Epigenetic changes, 718Epigenetics, 717Equatorial cell cortex, 213ERK1/2, 403

activation of, 135phosphorylation of, 142sregulation of, 135

ERK activity, 130, 318sustained, 136–137

ERK-MAPK pathway, 590ERK pathways, 735Errors, of mitosis, 214–223Erythroleukemia, 342Estradiol (E2), 730, 738Estrogen, 6Eukaryotic nucleus, 62–63Eukaryotic protein synthesis, mechanism of,

398–400Eukaryotic replication process, 36EVI1 protein, 274–275Exisulind, 733–734Exportins, 721Expression profiling, 691Extracellular matrix (ECM), 297–332, 725. See

also Cell-ECM interactions; ECM entriescomponent mutations, 299growth regulation by, 311tissue specificity of, 298–306, 306–310

Extracellular matrix receptors, non-integrin,304–306

Extracellular regulation, of cancer, 723–724Extracellular structures, cancer and, 725–727Extrinsic pathway activation, 511–512EZH2 gene, 274

INDEX 783

FADD (Fas-associated death domain) protein,140, 143, 503

Familial adenomatous polyposis coli (FAP) gene,712

Fanconi anemia, 557Farnesyl transferase inhibitors, 733Fas-Fas ligand mechanism, 752Feedback loops, E2F-mediated, 113–114FGF-2 mRNA, 419Fibril-forming collagens, 300Fibrillar center (FC), 30Fibroblast cultures, proliferative capacity of,

641Fibroblast growth factor 2 (FGF-2), 419Fibroblast growth factor (FGF) family, 582Fibroblast growth factor receptor (FGFR), 315Fibroblasts, senescent, 748Fission yeast. See Schizosaccharomyces pombeFission yeast cell cycle, 985¢-TOP sequences, 409–4105¢-untranslated region (5¢-UTR), 407, 408, 418,

419FKBP12 protein, 406Flavopiridol, 678–680, 686FLIP (FLICE-inhibitory protein), 140, 143Flow-FISH, 457–458FLT3 receptors, 736Fluorescent in situ hybridization (FISH),

457–458Fluoresence recovery after photo-bleaching

(FRAP), 63Focal adhesion kinase (FAK), 136–137, 313. See

also Integrin-FAK/Src pathwayactivation of, 314

Focal adhesion-mediated signaling, 313–314Folkman, Judah, 333Follicular lymphomas, 592Ford, Heide L., 95Fordyce, Colleen, 45148S complex, 3994E-BP1 protein, 404Frameshift mutations, 533, 534Frogs, metamorphosis in, 376–377. See also

Xenopus entriesFunctional cell cycle parameters, 690Fused replication proteins, 38

G0 cells, 138, 741G0 phase, 414G1 arrest, p53-dependent, 246G1 CDK-Rb-E2F pathway, proliferation control

and, 107G1 cyclins, 44, 413–414G1 (gap 1) phase, 4, 95, 96–97, 316–318

signal transduction pathways in, 130–137G1 phase cells, 5G1 regulation, 137–143


784 INDEX

G1ÆS phase cell cycle progression. See alsoG1ÆS phase transition

blocking of, 420proteolysis in, 155–156regulators affecting, 152–156signaling pathways in, 150–152translationally controlled proteins and, 417–420translational signals affecting, 413–421

G1ÆS phase transition, 103–114cell structure and gene expression at, 31–35cyclin-CDK complexes that govern, 238–240E2F transcriptional target control of, 109–111programmed gene expression at the R point

versus, 32–33retinoblastoma family, 610–612

G2 (gap 2) phase, 4, 95recruitment of mRNAs to polysomes in,

423–424G2 checkpoint, 122

DNA damage-induced, 121–124sensors and proximal signal transducers of,

122summary of, 123

G2ÆM damage checkpoint, 768G2ÆM phase checkpoint, 9G2ÆM progression, translational signals

affecting, 421–424G2ÆM transition, 114–124

control of, 215–217G2 nuclei, 179G2 phase cells, 6GADD45 protein, 122, 640, 769GADD genes, 733Gain of function

via mutations, 104targeting, 686

Gastric cancer, 679, 691Gastrointestinal stromal tumors (GISTs), 684,

685GC-1, 376GCN5/PCAF prototype, 268Geminin, 169, 170, 171Gene amplifications, 528Gene conversion, 56Gene duplication, 5Gene expression, 7, 20

A/Cdk2 in, 156architectural compartmentalization of, 22–23in cancer, 713–714genome packaging to accommodate, 39–43at the G1ÆS phase transition, 31–35patterns of, 297–298redistribution of nuclear proteins supporting,

48–49regulatory components of, 26S-phase related, 34serum factors and, 137

Gene expression/replication, regulatorycomponents for combinatorial control of,28–30

Gene products, roles in senescence, 748Gene promoters, 17Gene repression, 271

E2F-mediated, 109Genes

cell cycle-related, 690–691E2F regulated, 110inactivation of, 718mutated, 710R-point activation of, 33

Gene therapycancer, 430strategies for, 656–657

Genetic alterationsin repeated sequences, 533–534sources of, 527spontaneously arising, 709

Genetic disease, ECM and, 298–299Genetic regulation

of cell proliferation and growth, 386–387of programmed cell death, 383–386T3-mediated, 376–377

Genetic regulatory hierarchy, steroid triggeringof, 382–383

Genistein, 678Genome organization, 39–43

nucleosome and, 40Genomic instability

cancer and, 454telomere malfunction and, 453–454, 459

Genomic integrity, p53 and, 753Genomic niches, 42–43Germ cell tumors, 671Giordano, Antonio, 607Gleevec®/STI571/imatinib mesylate, 598, 736Global genomic repair (GGR), 535Global protein synthesis regulation, 412–413Glucocorticoid receptors, 20Glucose transporters (GLUT), 724Glycogen phosphorylase, 679Glycogen synthase kinase 3 (GSK-3), 401, 402,

677, 683Glycosaminoglycan (GAG) chains, 303Glypicans, 304, 306, 309GNAT superfamily, 268Go6976, 764, 768G protein coupled receptor (GPCR), 733G protein-coupled receptor kinases, 732Granular component (GC), 30Growth arrest, 753Growth control

cell cycle and, 669–703loss of, 669

Growth disregulation, 9–10


Growth factor beta (TGFb), 729–730, 737. Seealso TGFb-RII gene

Growth factor binding, 150Growth factor receptors, cooperation with

integrins, 315–316Growth factor/receptor tyrosine kinase (RTK)

signaling, 315Growth factors, 5, 103, 397–398

cancer and, 727–730CKI expression and, 105–106c-Src activation and, 590–591phosphatidylinolitol-3 kinase/Akt pathway

and, 591platelet-derived, 730role of, 150–151

Growth factor signaling, 39“Growth-regulated” mRNAs, 407Growth regulation, by ECM, 311Growth-related protein synthesis, 402Growth stimulation, 6Growth suppressive properties, retinoblastoma

family, 616–617Growth termination, in cancer, 745–751GTP (guanosine triphosphate), 731

binding of, 12GTPase-activating proteins (GAPs), 130Guanine nucleotide exchange factors (GEFs),

130, 588, 731“Guardian of the genome,” 9Guidi, Cynthia J., 265

H1 histone, 266phosphorylation of, 275

H2A histone, 276H2AX histone variant, 58H2B histone, 276H3 histone, 46–47

phosphorylation of, 275H4 genes

HiNF-P-dependent activation of, 35transcription of, 33

H4 histone, 33, 46–47H4/n locus, 47H23 lung tumor cell line, 623Hamartomatous tumorous growths, 387Hamster cells, Orc1 in, 163Hamster DHFR domain, ori regions of, 160Haploinsufficiency hypothesis, 712Harvey sarcoma virus, 583HAT activity misregulation, cancer and, 269–270Hayflick limit, 470, 641HBO1 histone acetyltransferase, 167hBRM subunit, 47HCT116 colon cancer cells, 648HDAC1, 614Head-and-neck cancer, 428Heat shock proteins (Hsp), 134, 720, 758–759

INDEX 785

hedgehog gene product, 374HeLa cells, 417, 422, 426Helicase activity, 166Hemangioendotheliomas, 352Hemangiomas, 352Hematological malignancies, 270Hematopoiesis, 61–62

RUNX1 protein and, 62Hematopoietic cells

apoptotic pathway subversion in, 593–595S6 phosphorylation in, 410

Hematopoietic stem cells, 61–62Hemidesmosome-mediated signaling., 313Hepatocellular carcinomas (HCC), 712Hepatocyte growth factor (HGF), 139Hepatocyte growth factor/scatter factor

(HGF/SF), 138, 727Hepatocytes, 139HER2 gene, overexpression of, 727Hereditary cancer, 711–712Hereditary nonpolyposis colon cancer (HNPCC),

530, 532, 533. See also Colon cancer; HNPCCtumor spectrum

Heritable DNA, structure of, 40Herpes simplex virus-1, 174Herpes thymidine kinase (HTK), 430Heterodimeric protein kinases, 115Heterodimerization, 475Heterogeneous malignant cells, response to

therapy, 771Heterotrimeric molecules, 300HIF-1 (hypoxia-inducible factor-1) alpha, 350Hinchcliffe, Edward H., 201HiNF-D complex, 35HiNF-M/IRF-2 complex, 35Histologically normal cells, telomere malfunction

in, 458–460Histone acetylation, 45–46, 267–271, 614

in cancers, 719Histone acetyl transferase HBO1, 167Histone acetyl transferases (HATs), 46, 108, 267,

719overexpression of, 270–271

Histone core particle, 40Histone cores, modification of, 41Histone deacetylation, 271–272Histone deacetyl transferases (HDACs), 46, 108,

608–609, 756. See also HDAC1; SIN3-HDACcomplex

categorization of, 271“Histone fold,” 266Histone gene expression

coupling with DNA replication, 32S-phase initiation transcriptional control and,

33–35Histone gene transcription factors, 33Histone H4, 744


786 INDEX

Histone methylases (HMTases), 46Histone methylation, 46, 272–275Histone modifying factors, 28–29Histone mRNAs, de novo synthesis of, 32, 33Histone Nuclear Factor P (HiNF-P), 35Histone octamer, 265–266Histone phosphorylation, 275Histone proteins, 40. See also H1–4 histone

entrieschromatin remodeling and, 45post-translational modifications of, 45–47

Histone synthesis, 767–768Histone tails, 266

hyperacetylation of, 267Histone ubiquitination, 276hMLH1 gene, 532, 533hMSH2 gene, 533HNPCC tumor spectrum, 532. See also

Hereditary nonpolyposis colon cancer(HNPCC)

Holometabolous insects, metamorphosis in, 369“Homeobox,” 374Homeodomain-interacting protein kinase-2

(HIPK2), 648Homeostatic cell death, 64Homogeneously staining regions (HSR), 585Homologous recombination (HR), 54, 551–556

cancer and, 556–558Homologue pairing, 22Hormones

control of metamorphosis by, 376–387metamorphosis-controlling, 373

Host cellular proteins, T antigen and, 472“Hot spot” mutations, 651, 652–653“Hox” genes, 374HPD tripeptide loop, 481Hsc70 chaperone, 477, 481–482HSIX gene, 746hSnf2H protein, 282hSWI/SNF complexes, 47–48hTERT subunit, 470, 471, 750Human b-globin gene, initiation of replication in,

160–161Human fibroblast proliferation, 641–642Human papilloma viruses (HPV), 712Human tumors, 337

isolation of dominant transforming genes from,582–584

p27 in, 251Hupki mice, 648–649Hyaluronic acid/hyaluronan (HA), 303Hydrogen bond bridges, 266Hydrophilic biomolecules, 721–722, 724Hydroxyurea (HU), 51, 175Hymenialdisine, 683Hyperphosphorylated pRb, 105Hypophosphorylated pRb, 105, 156

Id1 transcription factor, 340Id proteins, 746IGF binding proteins, 728IGF signaling pathway, 26IgH region, 549IkB kinase (IKK), 762, 763IkB protein, 688IL-2 expression, 142IL-2 transcription, 140IL-6 production, 139Ilyanassa obsoleta, programmed cell death and,

375Imaginal discs, 386–387Imatinib, 676, 680, 684–685, 686Imbalzano, Anthony N., 265“Immature” spindles, 220Immortalization

cell, 750defined, 469spontaneous, 470by SV40 large T antigen, 467–495

Immortalizing gene, 470, 471Immune cells, 140–143Immunoreceptor tyrosine activation motifs

(ITAMs), 141Immunotherapy, sensitizing leukemia cells to,

689Importins/exportins, 721Imprinting, 42Indirect-acting carcinogens, 586Indirect angiogenesis inhibitors, 345–347Indirubin, 682Indolinone derivatives, 684Infection, SV40-associated, 467ING1 tumor-suppressor, 59Inhibitor of apoptosis protein (IAP) family, 139,

499, 509, 512, 761, 762. See also X-linked IAP(XIAP)

Inhibitor production, 219Inhibitors of kinases (INK), 7, 742. See also Ink

cell cycle inhibitor familyINI1 gene, 279Initiation factors, 400Initiator caspases, 498Ink4a locus, 649Ink4 cell cycle inhibitor family, 105, 241, 318,

742Ink4 regulation, 154Ink cell cycle inhibitor family, 44. See also

Inhibitors of kinases (INK)members of, 242–245

Ink proteins, 252Insects, metamorphosis in, 369, 377–378Insulin

eEF2 and, 401elongation and, 401

Insulin-like binding protein-3 (IGFBP-3), 723


Insulin-like growth factor 1 (IGF-I), 5, 418, 728Insulin-like growth factor 2 (IGF-II), 728Insulin-like growth factors, 727–728. See also IGF

entriesInsulin-stimulated protein synthesis, 412–413Integrin clustering, 312, 313Integrin-FAK/Src pathway, 130. See also Focal

adhesion kinase (FAK)Integrin family, 298Integrin-linked kinase (ILK), 313Integrin-mediated adhesion, 316, 318Integrin-mediated signaling, 315

cell cycle regulatory targets of, 316–319Integrins, 303–304, 308–309

cooperation with growth factor receptors,315–319

Integrin signaling, 136–137, 304–305cell proliferation control by, 311–319cyclin D1 regulation by, 319

Integrin subunit mutations, 304Interferon alpha, 352, 689Interstitial/stromal matrix, 297int genes, 582Intracell localization, 12Intracell signaling, in cancer, 730–741Intranuclear targeting mechanism, 24, 25Intranuclear trafficking, linkage to developmental

arrest and leukemia, 25Intrinsic pathway, 512Intrinsic pathway dysregulation, cancer and,

509–510Invertebrate life cycles, 369–370IRES-driven translation, increase during M

phase, 422–423IRESes, 410–412Irradiation, DNA damage caused by, 154–155Isw1p protein, 281Isw2p protein, 281ISWI (imitation switch) subfamily, 281–282

Janus kinases (JAKs), 593, 595Jat, Parmjit S., 467J domain, 481–482Johnson, Roger D., 525JUN N-terminal kinase (JNK) cascade, 504Juvenile hormone (JH), 378–379Juvenile hormone active compounds, in larval

development, 378–379

K9-H3 methylation, 47Karyomeres, 213Keratinocytes, CKIs and, 253KI-67 protein, 5Kidney disease, 301Kinase cascades, 730–731

in cancers, 734–736Kinase domain, 575

INDEX 787

Kinases, 6polo-like, 121therapies directed against, 736–737

Kinase suppressor of Ras (KSR), 134Kinetochores, 120, 207–208

attachment to spindle, 218–221inhibitory activity produced by, 219saturation with attached microtubules, 220–221in the spindle checkpoint, 124

Kirsten sarcoma virus, 583KIT mutant mice, 686Knobloch syndrome, 343Knockout mice, 113, 243–245. See also Double

knockout mice; Triple knockout mouseembryonic fibroblasts (TKO MEFs)

Bax/Bak, 644Brm, 279–280cellular systems derived from, 254Mdm2, 647p27, 247–248p53, 654p57Kip2, 248–249p63 and p73, 638–639Puma, 644Rb, 617–618studies using, 242telomerase, 454

Koff, Andrew, 237K-ras genes, 752Ku binding, 55–56, 545–546Ku proteins, 766

Lamin B receptor (LRB), 63Laminin 5, 302Laminin alpha 2, 302Laminin beta 1, 302Laminin components, 302Laminin-rich basement membrane (lrBM), 302Laminin-rich reconstituted basement membrane

(lrBM), 316Laminins, 8, 301–302, 308Lamins, B-type, 177Lamin subunits, phosphorylation of, 118Large molecules, noncovalent regulation by, 12Large T antigen, 476. See also Small t antigen

cellular pathways affected by, 485mutational analyses of, 472N-terminal region of, 481p53 and, 479–480p63a proteins and, 484SV40 and, 471–472

Larval development, juvenile hormone activecompounds in, 378–379

LAT (linker for activation of T cells), 141LATS mutations, 387Laufer, Hans, 369Lethal (2) giant (l(2)gl) larvae, 386


788 INDEX

Leukemia cellsHL-60 promyelocytic, 46–47persistence in CML, 689–690sensitizing to immunotherapy, 689sensitizing to S-phase specific drugs, 688–689

Leukemia-related chromosomal translocations,28

Leukemias. See also Acute lymphoblasticleukemias; Acute myeloblastic leukemia(AML); Acute myeloid leukemia; Acutepromyelocytic leukemia (APL; PML);Erythroleukemia; Lymphomas

bcr-abl gene and, 585, 685chromosomal translocations in, 270linkage to intranuclear trafficking, 25monocytic, 268myeloid, 275reduced telomeric DNA and, 456SIN3-HDAC misregulation and, 271–272

Leukemia virus, activation of oncogenes by,578–581

Leukemiogenesis, 62, 272Li-Fraumeni syndrome (LFS), 101, 651, 655Lian, Jane B., 15“Licensing factor,” 179Life cycles, varieties in, 369–373. See also Cell cycleLinker DNA, 266Linker histone, 276Lipophilic molecules, 730Liver homeostasis, 138–140Liver regeneration, termination of, 139–140Liver stem cells, 139LMP2 proteasome, 45Lock, Rowena L., 467Locus control region (LCR), 160Loss-of-function mutations, 104, 307Loss of heterozygosity (LOH), 243, 459, 651, 709,

712–713LTR integration, 579, 582Lung cancer, 319, 428, 456LxCxE motif, 475, 476LxCxE viral oncoproteins, 608LY294002, 420Lymphomas, Mo-MuLV-induced, 579Lysine 9 of histone H3 (K9-H3), 46Lysine histone methyltransferases, 272–273

Macromolecules, nucleocytoplasmic transport of,63

Mad2 protein, 50, 124Mad genes, 221Mad (mitotic arrest defective) protein family, 50,

124transcriptional repression and, 271

Malignancies. See also Cancergenetic makeup of, 676–677human, 670

Mammalian CDKIs, 44Mammalian cell cycle, 318Mammalian cell fusion experiments, 149Mammalian cells

chromosome-based spindle assembly in, 207initiation of DNA replication in, 158–159viral genome replication in, 39

Mammalian SWI/SNF complexes, 278–280Mammals

cell growth and division rates in, 417G1ÆS progression in, 416–421

Mammary epithelial cells, 312, 454–455tumorigenic, 316, 317

Mandibular organs (MOs), 379Manduca sexta

ecdysone in, 380JH isoforms and, 379nitric oxide in, 375–376

Mantle cell lymphoma, 679MAP4 promoter, 640MAPK activation, 315. See also Mitogen-

activated protein kinases (MAPKs)MAP-kinase-kinase (MAPKK), 588MAPK-initiated differentiation., 314MAPK-interacting Ser/Thr kinases, 403–404MAPK isoforms, 588MAPK pathway, 275MAPK signaling, 313MAPK signaling pathways, 735, 751, 752Masciullo, Valeria, 607Maskin, 424Maspin, 740–741“Master regulator” transcription factors, 62Matrix-attached regions (MARs), 176–177Matrix metalloproteases (MMP), 740Maturation-promoting factor (MPF), 8, 115“Mature” spindle, 219MBD2 protein, 282–283MBD3 (methyl-CpG binding domain) protein,

282Mcm2 protein, 167MCM3 acetylating protein (MCM3AP), 167Mcm7 protein, 167–168Mcm10 protein, 167–168MCM complex, recruitment of, 169, 171MCM gene products, 165MCM proteins, 165–167

phosphorylation of, 171Mdm2 (murine double minute-2) gene, 751, 770

inactivation of, 649p53 regulation by, 646–647oncogenic potential of, 755

MDM2 protein, 475, 477, 479phosphorylation of, 650

MDS1-EVI1 gene, 274–275MEF2 target site, 46Mega-complexes, 173


MEK inhibitors, 752MEK/MAP kinase cascade, 749MEK regulation, 135MEL1 gene, 275Melanomas, 251, 680

familial cutaneous, 685Menon, Mani, 149Merosins, 302Messenger ribonucleic acids (mRNAs). See

mRNA entriesMetalloproteinase 9, 343–344Metamorphosing systems, genetic and molecular

control of, 374–375Metamorphosis

Drosophila, 380–387frog, 376–377hormonal control of, 376–387insect and crustacean, 377–378regulation by nitric oxide, 375–376regulation of cell growth, differentiation, and

death during, 369–395signals that control, 373studies of, 374–375tissue initiation of, 381

Metaphase, 115, 203, 210. See also M-phaseentries

Metaphase-anaphase transition, 211, 218blocking of, 221molecular changes of, 220

Metaphase plate, 209Metastasis, 10, 739–741. See also CancerMetastasis activators/suppressors, 739Metastasis-associated protein (MTA1), 739Metastatic tumors, 337Metazoans, replication origin models for, 162“Metronomic chemotherapy,” 349Mice. See also Knockout mice; Mouse entries;

Transgenic miceECM and ECM receptor mutations in,

308–309mutation engineering in, 113

Microsatellite instability (MSI), 530Microtubule nucleating complexes, 206Microtubules, 207Midbody, 213–214Mini-chromosome maintenance (MCM) proteins,

164, 165–167Mismatch repair (MMR) system, 528–534Mitochondria, apoptosis and, 759–761Mitochondrial mutations, 760–761Mitogen-activated protein kinases (MAPKs),

217, 731, 734. See also ERK-MAPKpathway; MAPK entries; Ras-Raf-MAPKpathway

Mitogenesis, 397–398Mitosis, 4, 6, 8, 201. See also Anaphase entries;

Antephase entries; Cell cycle entries; Cell

INDEX 789

division; Cycle phases; G0 entries; G1 entries;G2 entries; Metaphase entries; M-phaseentries; Prometaphase; Prophase; S-phaseentries; Telophase

cell architecture during, 118cell exit from, 119–121chromosome segregation during, 10delayed, 215, 216duration of, 218–219entry into, 205errors and quality control mechanisms of,

214–223events important in, 115multi-protein, nuclear-matrix-associated

complexes during, 49NPC proteins and, 64nuclear lamins and, 63phases of, 201–214phosphorylation events and, 117protein synthesis during, 422purpose of, 214stages of, 115

Mitotic arrest, 217Mitotic CDKs

inactivation of, 172in mammalian cells, 169–172

Mitotic checkpoint complex (MCC), 50Mitotic chromosomes, 21–22Mitotic cyclins, 43–44, 115–116Mitotic events, 201–235Mitotic progression, MCC and, 50Mitotic signals, FAK and, 313Mitotic spindle, drugs that interfere with, 671Mitotic spindle checkpoint, 49MKP-3 binding, 135MLL1 gene, 273MLL2 protein, 273MLL3 gene, 273–274MLL/ALL-1 gene, 270MMTV promoter, 275Mnk1/2 (MAPK-interacting Ser/Thr kinases),

403–404mob-5 expression, 733Model organisms, for cell cycle study, 97–99MOIH (mandibular organ inhibiting hormone),

380Molecular biology, of cycle phases, 6–8Molting hormones, 377–378Molt-inhibiting hormone (MIH), 378Mo-MuLV leukemia virus, 578, 579Monocytic leukemia, 268Monooriented chromosomes, 208

bipolar attachment of, 209Montecino, Martin, 15Mouse embryonic fibroblasts (MEFs), 454, 640,

641Mouse erythroleukemia (MEL) cells, 161


790 INDEX

Mouse mammary tumor virus (MMTV),activation of oncogenes by, 581–582

Mouse models, cell proliferation in, 306–310Mouse tumors, 337MOZ (monocytic leukemia zinc finger protein),

268–269. See also Zinc finger motifsMOZ oncogene, 270MPF (maturation promoting factor), 99M phase, 4, 8, 95. See also Metaphase

IRES-driven translation increase during,422–423

protein synthesis during, 421–422M-phase cells, 6M-phase promoting factor (MPF), 43–44Mre11/Rad50/Nbs (MRN) proteins, 55MRE11 complex, 546–547, 548, 551–553MRE11 protein, 57MRN complex, 55, 57, 58mRNA (messenger RNA), 5, 415. See also

Histone mRNAsAdoMetDC, 409cellular-IRES-containing, 411c-myc, 408cytoplasmic polyadenylation and, 423–424D1, 417, 418FGF-2, 4195¢-TOP, 409–410, 417“growth-regulated,” 407ODCase, 422–423oncogenes and, 713stability of, 116VEGF, 420, 427

mRNA-specific protein synthesis regulation,412–413

mRNA-specific translational control, 398cell cycle and, 407–413

MTA (metastasis-associated) protein, 282mtDNA (mitochondrial DNA), 760mTOR immunoprecipitates, 405mTOR inhibitors, 420mTOR kinase, 415mTOR pathway, blocking, 420–421mTOR protein, 406–407, 719

S6K1 activation by, 421Multienzyme complexes, 174Multiple endocrine neoplasia (MEN), 583Multiprotein complexes, 717mut genes, 530–531Mutations, 10

in cancer, 709–714checkpoint pathway, 215defective control of, 710–711gene, 713MCM10, 167in nonhomologous end-joining genes,

548–551proto-oncogene, 525–526

START, 414of tumor-suppressor genes, 58

Mutator phenotype, 711MutH protein, 530MutL homologues, 531mutS gene, 532

homologues of, 531Myc oncogene, 737–738. See also c-myc entriesMyc transcription factor, 112Myeloid leukemia, 275MyoD muscle-promoting factor, 619–620Myogenesis, 62MYST family, 268–269Myt1 kinase, 205

N-acetyltransferases, 268NAD+-dependent deactylase, 750Nascent DNA, 176NBS1 protein, inactivation of, 553NBS/Xrs1 protein, 57N-CoR (nuclear receptor corepressor), 272ND10 mechanisn, 39Negative feedback loops, E2F-mediated, 113–114NE-kB family, anti-apoptosis and, 762–763Neoplastic growth, 386Neuroblastomas, 654NFAT activation, 142NF-kB protein, 10, 508–509, 513, 759

activation of, 754overexpression of, 763

Nidogens, 302–303, 307, 308NIH 3T3 cells, 408, 417, 418, 425, 582–583

ODCase in, 419Nitric oxide, regulation of metamorphosis by,

375–376Noncovalent binding, 6, 12Nonhomologous end-joining (NHEJ), 54

defects in, 548of DNA double-strand breaks, 543–551

Nonhomologous end-joining genes, animalmodels with mutations in, 548–551

Non-integrin extracellular matrix receptors,304–306

Nonmalignant disorders, targeting cell cyclecomponents in, 691

Normal cells, telomere malfunction in, 458–460.See also Cell entries

Noxa gene, 644NPAT (nuclear protein mapped to the AT locus),

35NPC proteins, 64NRD (nucleosome remodeling and

deacetylating) complex, 282NSD1 gene, 274NSD3 gene, 274NSD proteins, 274N-terminus, 609–610


Nuclear architecture, 16components of, 19differentiation and, 61–62DNA replication and, 176–179gene expression and, 25

Nuclear envelope breakdown (NEB), 202, 203control of, 205–206

Nuclear envelope, cell cycle changes in, 62–64Nuclear lamins, 63, 64Nuclear localization signal (NLS), 609Nuclear matrix, gene localization and, 23Nuclear matrix targeting signal, 24Nuclear membrane

breakdown of, 179role in limiting replication, 179

Nuclear microenvironments, 19–20, 22–23Nuclear organization, 17

biological control and, 16–19Nuclear pores, 19, 65Nuclear proteins, dynamic redistribution of,

48–49Nuclear receptor-binding SET-domain containing

(NSD) family, 274Nuclear shrinkage, 65Nuclear structure

interrelationship with gene expression, 28replication foci attached to, 176–177

Nuclear substructure functions, 37Nuclear transcription, 63Nuclear transport/export signals, 58–59Nucleases, 10

degradation by, 11Nuclei, replication at fixed sites within,

178–179Nucleic acid-protein interactions, 21Nucleic acids, organization of, 16–30. See also

Deoxyribonucleic acid (DNA); DNA entries;Histone mRNAs; mRNA (messenger RNA)entries

Nucleolar cycle, 30–31Nucleolar localization signal (NoLS), 31Nucleolar organizer regions (NORs), 30–31Nucleolus, 20–21Nucleoplasmic transcriptional factors, 31Nucleosomal histone amino-termini, acetylation

of, 45–46Nucleosome, 40, 266Nucleosome organization, 18–19

water molecule and ion role in, 266Nucleotide excision repair, 534–538Nucleotide metabolism, regulation of genes

involved in, 35Nucleotide sequence changes, 527Nucleus regulatory machinery,

compartmentalization in, 19–23Nucleus-to-ECM signaling, 311, 314–315NuMA protein, 207

INDEX 791

NURD (nucleosome remodeling and histonedeacetylation) complex, 282–283

NURF (nucleosome remodeling factor), 281Nutrition-sensitive “gatekeeper,” 407

ODCase gene, 418ODCase mRNA, 422–423OGG1 glycosylase, 539, 542Oligodendrocytes, 254Olomoucine, 682Oncogenes, 268, 571–606, 710

apoptosis and, 592, 593–595cell cycle checkpoint subversion by, 595–598chemical carcinogens and, 585–587chromosomal abnormalities and, 584–585leukemia virus activation of, 578–581mouse-mammary-tumor-virus–induced

activation of, 581–582pro-angiogenic, 345retroviral-mediated activation of, 573–578role in switch to angiogenic phenotype,

344–345as targets for anticancer drugs, 345–347, 676viral and cellular, 571–573

Oncogenic stress, 244Oncogenic translocation, 550Oncoproteins, function of, 587–598Onyx-015 adenovirus, 657Oogenesis, vertebrate, 423Open chromatin state, 108Open-reading frames (uORFs), 408–409, 415OPG receptor, 503Orc1 homology regions, 164ORC binding, 164ORC proteins, 163Ori-b region, 161“Origin loading factors,” 164Origin recognition complex (ORC), 163–164, 744Origins of replication, 157–158. See also Ori

regionsOri regions, 157

in hamster DHFR domain, 160transcription/replication relationship in,

161–162Ornithine decarboxylase (ODCase), 419. See also

ODCase entriesOsteoclastogenesis, 62Osteopontin, 141Ovarian cancers, 60, 712

p14ARF protein, 59, 243, 244, 757. See also ARFproteins

p15Ink4b protein, 241, 244–245p16Ink4a knockout mice, “pure,” 244, 251p16Ink4a protein, 241, 242–244p16 protein, 622p18Ink4c protein, 241, 245


792 INDEX

p19Arf protein, 251, 252. See also Arf entriesp19Ink4d protein, 241p21 gene, 101–102p21 protein, 9, 105, 106, 117–118, 122, 242, 319,

639–640“assembly factor” role of, 246

p21Cip inhibitor, 245–246sequestering of, 252

p21Cip1/Waf1/Sdi1 protein, 478–479p21WAF1/CIP1 inhibitor, 53p27Kip1 inhibitor, 154, 246–248

sequestering of, 252as a tumor suppressor, 250

p27 protein, 44, 105, 106, 319, 596, 613, 687–688role in differentiation, 254

p27Xic expression, 254p38 MAPK, 733p38 pathway, 217p53AIP1 (p53-regulated apoptosis-inducing

factor) protein, 644–645p53 “hot spot” mutations, 652–653p53-negative cells, 751, 768, 769p53 pathway, 650

therapeutic targets in, 656–659p53 phosphorylation, E2F-1 and, 757p53 protein, 9, 11, 59, 101, 122, 279, 477–480. See

also Wild-type p53 proteinaging and, 747–748alternative splicing of, 637apoptosis and, 753–755inactivation of, 651–654mutation of, 651, 654post-translational modifications of, 647–648reactivation of, 657replacement of, 513retinoblastoma family interaction with,

613–614stabilization of, 123telomere malfunction and, 453–454as tumor suppressor, 31, 642–646upstream regulators of, 649

p53 target genes, 639p53 transactivation response, 645p53 tumor-suppressor genes, 635–666

apoptotic pathway initiation and, 642–646cell cycle control and, 639–640cellular senescence and, 640–642functioning of, 639–646regulation of, 646–651tumorigenesis and, 651–656

p53 tumor-suppressor protein family, 504–505p57Kip2 inhibitor, 248–249

loss of, 254p63a proteins, 484p63 protein, 483–484, 636, 638p73 protein, 483–484, 636, 638, 755–756p107 gene, 114

p107 protein, 104, 475–476, 608, 610, 611, 612, 616,623–625

role in apoptosis, 619p130 protein, 104, 475–476p300/CBP, 270p300 histone acetyltransferase, 269, 270, 482–483Paclitaxel, 674Pancreatic cancers, 251, 338Papilloma virus, 471, 476Parasitic organisms, life cycles of, 372Parc (p53-associated parkin-like cytoplasmic

protein), 654Pardee, Arthur B., 3, 707PARP (poly(ADP-ribose) polymerase), 539, 541,

766, 769, 770PARP1, 542–543Patient population, defining, 685–686Paullones, 683–684PC12 cells, 314P chromosome movement, 212PD-ECGF (platelet derived endothelial growth

factor), 346PDGF-b receptor, 714PEA3 (polyome enhancer activator 3), 315Perichromosomal space, 41Periodic protein turnover, 43–45Perlecan, 303PERP protein, 642–643“PEST” sequences, 155Phase-specific arrest, 53–54PHAS-I (phosphorylated heat- and acid-stable

substrate regulated by insulin) protein, 403,404–405, 425, 426

manipulation of the expression of, 426–427mTOR and, 406, 407

Philadelphia chromosome, 584, 585Phorbol, 687Phosphatidylinositol 3-kinase/Akt pathway,

growth factors and, 591. See also Akt proteinfamily

Phosphatidylinositol 3-kinase (PI3-kinase) family,51–52, 55

Phosphatidylinositol-dependent kinase-1(PDK1), 403, 591

Phospho-inositide kinases, 122Phosphoinositol 3-kinase (PI3K), 413, 420, 508,

735Phosphorylation, 7, 110

ATM-dependent, 52Cdk1, 116–117of D1 and E cyclins, 44eIF4E, 403–404MPF-mediated, 43–45of retinoblastoma family members, 610

Physiological regulatory signals, nucleararchitecture and temporal-spatial integrationof, 26–27


PI3-kinases. See Phosphatidylinositol 3-kinaseentries; Phosphoinositol 3-kinase (PI3K)

Pic1 mutation, 154Picornaviral IRESes, 410PIDD expression, 643PIG genes, 645PIKKs (phosphatidylinositotal kinase-related

kinases), 406PIN lesions, 760Pituitary intermediate lobe hyperplasia, 248Pituitary tumors, 249, 250PKA kinase, 141PKB, 426PKB-mediated phosphorylation, 406PKC (protein kinase C), 151, 378, 379, 413, 680,

736, 737PKC isoforms, 402–403PKC signaling, 141PKR, 425Platelet-derived growth factor receptor

(PDGFR), 315, 587, 590, 590PLC (phospholipase C), 150, 152

activation of, 150, 151PLGF (placenta like growth factor), 346PLK1 protein, 121Ploidy-specific DNA repair, 54–55PLZF (promyelocytic leukemia zinc finger), 272.

See also Zinc finger motifsPLZF-RAR fusion protein, 272PML bodies, 20PML (promyelocytic leukemia gene) protein, 59,

417–418PML-RARA fusion protein, 675–676PML-RAR translocations, 272Pocket protein transcriptional repression, 615Pocket region, Rb family, 608–609Point mutations, 711Polar ejection force, 208Poleward (P) forces, 208, 210Poliovirus RNA translation, cap-independent,

422Polo-like kinase (PLK), 121, 211Poly(A) tracts, 423–424Polycomb (PcG) proteins, 273Polypeptide elongation, 401Polysome loading, 422Porter, Joseph F., 129Positive feedback loops, 240

E2F-mediated, 113–114Postmitochondrial death process inhibition,

cancer and, 510Postmitotic neurons, 249Post-transcriptional regulation, 109

in cancer, 719–720Post-translational mechanisms, 43PP2A phosphatase catalytic subunit, 416,

480

INDEX 793

pRb2/p130 protein, 607–608, 610, 611, 612, 613,616, 617, 623

role in apoptosis, 619pRB-complexes, 482pRB-E2F complex, 477pRb/p105 protein, 616, 617, 622–623

embryos deficient in, 617PRDX3 gene, 761Pre-replication complex (pre-RC), 99, 162

assembly and activation of, 169–172cell cycle regulatory events controlling, 170formation of, 180proteins associated with, 168–169

Pre-RNA processing, 11Prima-1, 657–659Pro-angiogenic oncogenes, 345Pro-angiogenic proteins, 346Pro-apoptotic therapy, 763–765Prognosis, cell cycle parameters and, 690–691Programmed cell death (PCD). See Apoptosis;

Autophagic programmed cell death;PUMA (p53 upregulated mediator ofapoptosis)

Programmed gene expression, temporal-spatialidentity of, 32–33

“Proinflammatory syndrome,” 679Proliferating-cell nuclear antigen (PCNA), 37, 38,

157, 167, 177, 478)p21 and, 246

Proliferation. See also Cell proliferationof cancer cells, 722–723coordination of, 714

Proliferation/differentiation cell cycle control,60–62, 716

G1 CDK-Rb-E2F pathway and, 107Proliferative fate, 237Proliferative regulation, 9, 103Prometaphase, 203, 206–210Promyelocytic leukemia, 20Prophase, 115, 202–206Prostate cancer, 733Prostate hyperplasia, 250Prostate tumorigenesis, 455Pro-survival signaling, cancer and, 508–509Proteasome inhibitors, 351, 688Proteasomes, 687

in cancers, 720regulation of, 44–45

Protein-DNA, scaffold-associated, 29Protein-DNA interactions, 17–18Protein kinase C. See PKC entriesProtein metabolism and distribution cycle,

43–48Protein phosphatases, 142Protein phosphorylation, 7Protein-protein interactions, 18

RUNX proteins and, 28


794 INDEX

Proteins. See also Enzymes; Histone entries;Oncoproteins

angiogenic, 335in asymmetric cell kinetics, 61bi-functional, 37–38cell cycle inhibitory, 237–264coregulatory, 26, 27degradation of, 11DNA-synthesis-associated, 156–157functional diversity and selectivity of, 755localization at DNA replication sites, 177mitochondrial, 761nucleolar-associated, 21peaks of incorporation into, 422pro-angiogenic, 334–335redundancy between, 249replication checkpoint and, 51retinoblastoma family of, 473–477selective trafficking of, 24translationally controlled, 417–420

Protein scaffolds, 142Protein stability, 116Protein synthesis

cancer and deregulation of, 425–430cell division and, 397–398growth-related, 402mechanism of, 398–400in M phase, 421–422regulation of, 412–413stages of, 398–400

Protein synthesis factorscancer therapy and, 429–430manipulation of the expression of, 425–427regulation of, 400–407

Protein turnover, selective and periodic, 43–45Protein tyrosine kinases, 734Proteoglycans, 303, 308Proteolysis

in cell cycle progression, 155–156initiation of, 720ubiquitin-dependent, 155

Proteosome, 7Prothoracotropic hormone (PTTH), 378Proximal signal transducers, G2 checkpoint,

122–123PS-341, 688PTEN tumor suppressor, 314, 510, 513, 650, 735–736PTP-1B phosphatase, 314PTP-PEST phosphatase, 314PubMed, 708PUMA (p53 upregulated mediator of apoptosis),

644, 753–754Puma gene, 644, 645–646Punctate sites

nuclear, 36protein complex organization at, 36–37

Purvanalol, 684

Quality control mechanisms, of mitosis,214–223

Quercetin, 678Quiescence

in cancer cells, 722Rb/E2F complexes and, 108

Quiescent (G0-phase) cells, 5, 104p27 in, 247

R337H mutation, 655–656Rac1, 764Rac pathway, 316rad9 mutants, 101RAD50 protein, 57, 547RAD51B gene, 557RAD51 mutation, breast cancer and,

556–557RAD51 nucleoprotein, 56–57, 553–554

BRCA2 and, 556RAD52 nucleoprotein, 56–57, 553, 554RAD54 protein, 56Radiolabeled nascent DNA analysis method,

159–160Raf-1 cycle, 133Raf-1 kinase activity, 132–133Raf-1 phosphorylation sites, 134Raf-1 protein, regulation of, 134Raf kinase inhibitor protein (RKIP), 134–135Raf kinases, 132–133RAG1/RAG2-induced DNA double-strand

break, 549Rapamycin, 405, 406, 410, 412–413, 419

5¢-TOP mRNAs and, 409inhibitory effects of, 420–421low-dose, 429–430TOR genes and, 415

Raptor protein, 406–407RARE (retinoic acid response element)

sequences, 272RAR locus, 20RAR regulators, 271–272Ras, cancer and, 731–734Ras activation, 150Ras binding domain (RBD), 132Ras cycling, 130Ras domains, 132Ras expression, oncogenic, 597–598Ras-GDP complex, 131Ras GEFs, 588Ras gene mutations, 732RasGRP (guanine nucleotide releasing protein),

141Ras GTPase activity, 131–132Ras-induced arrest, 749ras mutant, 710ras oncogene, 345ras protooncogenes, 584


Ras-Raf-MAPK pathway, 150, 152. See alsoMitogen- activated protein kinases(MAPKs)

Ras-Raf-MEK-ERK pathway, 130–136, 318Rat PHAS-I, 404Rb1 gene, 473Rb2 gene, genomic mutations of, 623RB2/p130 down-regulated genes, classification of,

624Rb/E2F, transcriptional target repression by,

107–109Rb family members, 104–105Rb gene, 103–104, 741, 743

control of E2F transcriptional activity and,107–109

regulation by cyclin/Cdks, 105–106restriction point and, 106–107

Rb mutant genes, 105rDNA genes, 161

in nucleolar structure, 30Reactive oxygen species (ROS), 759, 760Receptor tyrosine kinases (RTKs), 130–131, 315,

316, 588, 589RECK transcription, 740Recombinant human ORC subunit studies,

163–164Recombination, homologous, 551–556Recombinational repair substrates, 544–545RecQ helicases, 557–558Reddy, E. Premkumar, 571Reddy, G. Prem-Veer, 149Redundant angiogenic promoters, 350Regulation. See also Protein synthesis;

Regulatory proteinsp53, 646–651of protein synthesis factor activity, 400–407of ribosomal biogenesis, 30–31yin-yang principle of, 12

Regulatorsof angiogenesis, 334–335of apoptosis, 513

Regulatory cascades, 65Regulatory complexes, 16

assembly of, 66compartmentalization of, 19formation of, 19–23

Regulatory foci, architectural versus activity-driven assembly of, 25–26

Regulatory hierarchy, genetic, 382–383Regulatory proteins, 7

intranuclear organization of, 16–30Regulatory signals

hormone-responsive integration of, 20physiological, 26–27

Relief of dependence, 215, 217Rel proteins, 509Renal carcinoma, 679

INDEX 795

Repair checkpoints, DNA damage and, 766–769Replication, 129

controlled, 709at fixed sites within nuclei, 178–179genetically determined origins of, 160relationship with transcription in an ori region,

161–162role of nuclear membrane in limiting, 179

Replication checkpointsarchitectural features of, 51structural cycles of, 51–52

Replication complexes, DNA synthesis enzymesin, 172–175

Replication domains, in situ assessment of, 36Replication errors, 533Replication factor C (RF-C), 167“Replication factories” model, 37, 172, 177Replication foci

assembly and reassembly of, 38–39in S-phase cells, 176–177

Replication fork complex (RFC), 64, 176Replication intermediates, structural preservation

of, 51Replication origin function, chromosomal context

of, 160–161Replication origin models, for metazoans, 162Replication origins

DNA synthesis initiators at, 162–172“firing” of, 36

Replication protein A (RPA), 37Replication/repair domains, 21Replication sites, 36–37

cyclical parameters of, 37–39Replication zones, differential timing of, 42Replicative cellular senescence, 244, 641Replicon clusters

nuclear organization of, 178–179replication in, 176

Replicon model, 157Replitase, 36, 173Replitase complexes, 21, 175, 744

enzyme activities associated with, 174“Reserve cells,” 619Restriction fragment analysis, 159Restriction point (R), 5, 9, 32, 33, 96–97, 130, 137,

416, 473, 596, 742–743Rb and, 106–107

Ret gene, 583RET protein tyrosine kinase, 734Retinoblastoma (pRb) family of proteins, 607,

743, 753angiogenesis and, 621–622apoptosis and, 618–619deregulation of, 622–625development and, 617–618differentiation and, 619–621functional characteristics of, 610–616


796 INDEX

growth suppressive properties of, 616–617phosphorylation in, 610structural characteristics of, 608–610transcription factors associated with, 620

Retinoblastoma susceptibility gene product(pRb), 670. See also Retinoblastoma tumor-suppressor protein (pRb)

Retinoblastoma susceptibility protein, isolationof, 104

Retinoblastoma tumor-suppressor protein (pRb),7, 59–60, 103, 278, 473. See also Rb entries;Retinoblastoma susceptibility gene product(pRb)

cellular proliferation and, 271interaction with p53, 613–614phosphorylation of, 105, 156as tumor suppressor and proliferation

regulator, 103, 104Retinoblastoma tumor-suppressor protein (pRb)

family, 168, 473–477inactivation of members of, 107phosphorylation/inactivation of members of,

595–596, 612Retinoic acid receptors (RAR), 746. See also

RAR entriesRetinoic acids, 746–747Retroviral-mediated activation, of oncogenes,

573–578Retroviral transforming genes, 574Retroviruses, multiple transforming, 598Rh30 cells, 430Rhabdoid tumor, 279Rhoads, Robert E., 397Rho GTPase, 732–733Ribonucleotide reductase, 420Ribosomal biogenesis, 30

remodeling of regulatory machinery of,30–31

Ribosomal gene expression, 20–21Ribosomal protein S6, 405–406Ribosomal RNA gene (rDNA), 161Rieder, Conly L., 201RING domain, 60Rizki, Aylin, 297RIZ proteins, 274–275RNA (ribonucleic acid). See also mRNA entries;

rRNA genesantisense, 417, 419secondary structure of, 408

RNA polymerases, 30RNA tumor viruses, 571, 572Roscovitine, 682Rothmund-Thompson syndrome, 558Rous sarcoma virus (RSV), 571, 572RPA protein, 39RPA protein complex, 553–554R point, 171

temporal-spatial identity of programmed geneexpression at, 32–33

rRNA genes, transcription of, 30RSC complex, 280–281RSF (remodeling and spacing factor), 282Rubenstein-Taybi Syndrome (RTS), 270Runx/Cbfa/AML transcription factor, 29RUNX-containing regulatory complexes, 20RUNX intranuclear targeting signal, 24RUNX proteins, 19–20, 24, 49RUNX transcription factors, 23, 24, 28RUNX1 protein, hematopoiesis and, 62RUNX2 protein, 25Ruv complex, 554

S6 ribosomal protein, 405–406S6K1 (S6 kinase 1), 405, 407

mTOR activation of, 421S6K1 activation, 5¢-TOP mRNAs and,

409–410S6K2 (S6 kinase 2), 406Saccharomyces cerevisiae, 97. See also Yeast

entriesCdc6 in, 164CDC45 gene mutation in, 168origins of replication in, 158replication in, 163translation in G1ÆS progression in, 413

S-adenosylmethionine decarboxylase(AdoMetDC) mRNA, 409

Salivary gland autophagic cell death, 384–385transcription increases and, 386

salvador (sav) gene, mutations in, 387SaOs2 osteosarcoma cell line, 616, 619, 624Scaffolding nuclear proteins, 29, 48–49Scheduled nucleocytoplasmic shuttling, tumor-

suppressor proteins and, 58–59Schizosaccharomyces pombe, 95, 97–98. See also

Yeast entriesCdc18 in, 164replication origins in, 158

scid cells, 56Sclafani, Robert A., 95Securin (Pds1), 50, 120, 121, 211Selective protein turnover, 43–45Senescence, 470

endothelial cell, 348p21Cip and, 246

Sensors, G2 checkpoint, 122–123Separase (Esp1), 50, 211Serine-15 (S15), phosphorylation of, 647Serine proteases, 740Serine/threonine kinases, 132, 135, 734Serum-stimulation, 137SET-domain-containing proteins, 275SET domains, 272–273, 274SET subfamilies, 273–274


7-Hydroxystaurosporine, 680–682Severe combined immunodeficiency (SCID), 546,

548SH-2 (Src homology 2)-containing adapter

proteins, 130SH2 domain, 575Shc protein, 313, 314Shrimp, developmental stages of, 371Signaling, centriole-based, 214Signaling mechanisms, architectural

compartmentalization of, 26Signaling molecules, upstream of translation, 427Signaling pathways, 151, 402

in cell cycle progression, 150–152Signal transduction, 6, 7

G2 checkpoint in, 122–123Signal transduction pathways, 130–137Silver-stained NORs (AgNORs), 31Simian virus 40 (SV40), 467–485. See also SV40

entriesSimian virus 40 (SV40) large T antigen, 750

immortalization by, 467–495Sin3a corepressor, 478SIN3-HDAC complex, 271–272. See also Histone

deacetyl transferases (HDACs)SIN3 protein, 272Single-strand annealing (SSA), 56, 57–58Sister chromatids, 115separation of, 119–121“Sister” kinetochores, 208, 210Skeletal development, perturbations in, 20Skin disease, 304, 307Slot blotting, 457Sluder, Greenfield, 201SMAC apoptogenic factor, 513SMAC/DIABLO apoptogenic factor, 505, 759,

761SMAD coregulatory factor, 26–27Smad transcription factors, 244Small-molecule transcription activation,

738–739Small t antigen, 480. See also Large T antigen“Smart virus,” 657SMRT (silencing mediator for retinoid and

thyroid receptors), 272SNF5/INI1 subunit, 279SNF (sucrose fermentation) protein, 277–278Solid tumors, 671, 721

growth of, 723telomere length and, 456

Sotos syndrome, 274Species, commonalities among, 421S phase, 4, 95, 96

cellular preparation for, 179–180CKI involvement in, 154duration of, 42gene expression at the end of, 156

INDEX 797

independent cycle integration in, 38protein complexes and, 36–37

S-phase cells, 5replication foci in, 176–177

S-phase checkpoint, 9S-phase cyclin/Cdks, 157S-phase initiation, transcriptional control at,

33–35S-phase replication checkpoint, 49–50S-phase replication origin, “firing” in, 36S-phase specific drugs, sensitizing leukemia cells

to, 688–689S-phase specific nuclear microenvironment, 37–39Spindle

chromosome attachment to, 208kinetochore attachment to, 218–221

Spindle assembly, 207Spindle bipolarity, 206–207Spindle checkpoint, 50, 101, 123–124, 125, 218Spindle multipolarity, 221, 222Spindle poles, motive force for separating,

212–213Spindle pole separation, force-producing

mechanism for, 203–205Spontaneous immortalization, 470Src family kinases, 313

activation of, 141src oncogene, 345, 572, 590, 734Src oncoprotein, 575START mutants, 414START point, 9, 97, 171, 413, 414STAT proteins, 593–595“Status quo” hormone, 378Staurosporine, 8, 680–682Stein, Gary S., 15Stein, Janet L., 15Stem cells, 61maintenance of, 61Sterile alpha motif (SAM) domain, 484Steroid hormones, 6, 377Steroid regulatory hierarchy, 382–383Strand invasion, 57Stress, p53 and, 646–651Stressed cells, cancer and, 765–769Structural maintenance of chromosome (SMC)

proteins, 41, 547SU9516, 684Subcellular localization, CyclinB/Cdk1 activity

and, 117Subnuclear domains, 19Subnuclear localization, of RUNX transcription

factors, 25Subnuclear targeting, 59Sulindac, 733–734Suppressed chromatin template, 40–41Suppressor of Ras-8 (SUR-8), 134Survivin, 139, 509, 512


798 INDEX

SUV39H1/2 methyltransferase, 273SUV39 subfamily, 273SV40 genome, gene products associated with,

468. See also Simian virus 40 (SV40) entriesSV40-immortalized cells, 480SV40 oncogene, 338, 339–340SWI2/SNF2 subfamily, 276–281SWI (switching) protein, 277–278SWI/SNF complexes, 555

mammalian, 278–280Swiss 3T3 cells, 416Switches, physiologically responsive, 45–47Syndecans, 303, 304–306, 309

T24 bladder carcinoma cell line, 583T antigens, 468, 469, 471Tap42 protein, 415–416tap42-11 mutant, 416Target genes, transrepression of, 640Targets. See also Therapeutic targets

defining, 685physiological function of, 686

Target-specific therapies, cell cycle, 675–684Tau proteins, 683Taxol, 216T-cell proliferation, 140–143T-cell response, 689TCR/CD3 complex, 141, 142TCR receptor, 143Telomerase activity, 749–750Telomere-associated sequences (TAS), 451–452Telomere content, measuring, 457Telomere length, cancer prognosis and, 455–456Telomere malfunction

carcinogenesis and, 454–455genomic instability and, 453–454in histologically normal cells, 458–460

Telomere repeat factor 1 (TRF1), 452Telomere repeat factor 2 (TRF2), 747Telomere restriction fragment length, 457Telomeres

composition and structure of, 451–453quantification of, 456–458senescence and, 749shortening of, 470

Telophase, 115, 203, 213–214Testicular cancer, 342Tetraploid cells, homologous recombination in,

56–57TFIIH protein, 538TGFb-RII gene, 534. See also Growth factor beta

(TGFb)Therapeutic targets, in the p53 pathway, 656–659.

See also TargetsTherapies

kinase-directed, 736–737pro-apoptotic, 763–765

target-specific, 675–68430-nm chromatin fiber, 40TH receptors (TRs), 3763T3 cells, 710Threonine 14 (Thr14), 116, 117Threonine 161 (Thr161), 116, 117Thrombospondin, as an angiogenesis inhibitor,

341–342Thrombospondin-1, 341–342, 621, 726Thymidylate synthase (TS), 175, 420Thyroid hormone (TH), 376–377Thyroid-stimulating hormone (TSH), 376Thyroid tumors, canine, 333Thyroxine, in frog metamorphosis, 376–377Tie-2 receptor, 355Tip41 protein, 416Tissue-specific gene expression patterns, 297–298TLE/Groucho coregulatory proteins, 27T-loop, 116, 452Tlsty, Thea D., 451TNFa protein, 139, 764TNP-470 chemotherapeutic agent, 335–336, 347tumor types inhibited by, 337TOR genes, 414–415TOR pathway, 414–415

effect on translation initiation, 415–416“Traction mediated cytofission,” 214TRADD (TNFR-associated death domain), 503Trafficking signals, 24trans-acting factors, 398–399, 408, 410trans-acting proteins, 157. See also DNA synthesis

initiatorsTransactivation (TA) domain, 636Transcription, 11

eIF4E gene, 405relationship with replication in an ori region,

161–162Transcription activating factors (TAFs), 646Transcription activation, by small molecules,

738–739Transcriptional co-activators, 269Transcriptional control

biochemical components of, 16–17at S-phase initiation, 33–35

Transcriptional intermediary factor 2 (TIF2),270

Transcriptionally active chromatin template,40–41

Transcriptional machinery, chromatin structureand, 267

Transcriptional regulation, 43CBP proteins and, 483

Transcriptional targets, 23–25Rb/E2F repression of, 107–109

Transcription coupled repair (TCR), 535Transcription factor organization, disease and,

62


Transcription factors, 6, 716associated with retinoblastoma family, 620coregulatory proteins and, 29at gene regulatory foci, 32interaction with ORC, 168as “scaffolding proteins,” 48

Transferrin, 5Transgenic mice

cyclin D1, 152tumor cell implantation into, 341

TranslationIRES-dependent, 410signaling molecules upstream of, 427

Translational control, 11, 398cell cycle and, 397–448mRNA-specific, 407–413

Translationally controlled proteins, G1ÆSprogression and, 417–420

Translational signalsG1ÆS progression and, 413–421G2ÆM progression and, 421–424

Translation initiation, TOR effect on, 415–416Translocations, analysis of, 549Trichostatin A (TSA), 615Tricothiodystrophy (TTD), 538Triple knockout mouse embryonic fibroblasts

(TKO MEFs), 612TSC1/2 mutations, 387“T/t common region,” 468Tuberous sclerosis, 387Tumor aggressiveness, 250–251Tumor angiogenesis, 333–353Tumor cell proliferation, 341Tumor cells

genomic alterations in, 347–348resistant, 347restoring apoptosis to, 758–759

Tumor growth, angiogenesis dependence of,335–344

Tumorigenesis, 525–526, 710nucleolar structure and, 31p53 and, 651–656safeguards against, 49–54

Tumor necrosis, 350Tumor necrosis factor receptor (TNFR)

superfamily, 142–143, 498, 502–504, 506, 511,642. See also TNFa production; TRADD(TNFR-associated death domain)

Tumor-necrosis factor-related apoptosis-inducingligand (TRAIL), 503, 511–512

Tumor-producing acute transforming viruses, 572Tumor progression, 10

role of angiogenesis in, 350Tumor regression, 350Tumors. See also Human tumors

avascular, 340centrosome amplification and, 222

INDEX 799

drug-resistant, 348–349growth of, 715inhibited by endostatin, 338inhibited by TNP-470, 337treating, 656–659uncontrolled cell division in, 58VEGF expression by, 334

Tumor-suppressor functions, restoration of, 657Tumor-suppressor gene cycle, 58–60Tumor-suppressor proteins, 59–60

regulation of, 59scheduled nucleocytoplasmic shuttling and,

58–59subnuclear targeting and, 59

Tumor-suppressor regulation, nucleolus and, 31Tumor suppressors, 9, 104, 250, 251, 270, 278–279,

280, 477, 504. See also p53 proteinclassification of, 636–639intranuclear compartmentalization of, 60nucleolar sequestration of, 59–60retinoblastoma protein as, 103

Tumor syndromes, familial, 656Tumor vessels, 333Tumstatin, 343–34426S proteasome, 44, 45, 687Two-dimensional gel analysis method, 159–160Tyrosine 15 (Tyr-15), 116, 117, 122Tyrosine kinase inhibitor, 346“Tyrosine kinome,” 686

Ubiquitin-activating enzyme (E1), 119, 155Ubiquitin-conjugating enzyme (E2), 119, 155Ubiquitin-dependent protein degradation

complex, 172Ubiquitin-dependent proteolysis, 171–172Ubiquitin ligase enzyme (E3), 119, 155Ubiquitin ligases, 43Ubiquitin protein, 7Ubiquitin proteolysis pathway, 119UCN-01, 680–682, 687ultra bithorax (UBX) mutation, 374Ultraspiracle (USP) receptors, 379uORFs, 408–409, 415usp mutants, 382UV-DDB protein, 535

v-abl gene product, 576van Wijnen, André J., 15Vascular endothelial cells, genetic stability of,

347–348Vascular endothelial growth factor (VEGF),

334–335, 339, 350, 420, 621–622, 723V(D)J recombination, 55, 543, 546, 548, 549VEGF mRNA, 420VEGF protein-to-mRNA ratio, 427VEGFR (VEGF receptor), 725Velcade, 351


800 INDEX

Vertebrate oogenesis, 423vestigial gene, 375VHL (von Hippel-Lindau gene) protein, 59vHMEC cells, 455Viral DNA replication, 467–468Viral functions, J domain and, 481Viral genome, replication in mammalian cells,

39Viral oncogenes, 571–573Viral oncogenic proteins, 104, 476Viruses, cancer, 712–713v-myb oncogene, 579v-Myb protein, 577v-(virus) oncogenes, 574VP gene products, 468v-raf oncogene, 588v-ras oncogene, 583V-Ras proteins, 577v-src oncogene, 596

Waf1 mutation, 154“Wait anaphase” signal, 124Wang, Shulin, 497WARTS mutations, 387Water molecules, in nucleosome structure,

266WCRF complex, 282Wee1 gene, 98Wee kinases, 117, 205Werner’s syndrome, 558, 747White blood cells, telomere loss in, 458–459Wild-type mice, tumors in, 343, 344Wild-type p53 protein, 154–155, 651structure of, 653Wilm’s tumors, 248, 274wingless gene, 375Wnt pathway, 728–729Wolf-Hirschhorn syndrome (WHS), 274Wortmannin, 405Wound healing, 61WRN helicase, 558

WSTF (Williams syndrome transcription factor)protein, 282

X-chromosome inactivation, 42Xenopus laevis

B/Cdk1 activity in, 115Cdc45 homologues in, 168Cdc6 binding in, 164CDK inhibitors in, 254CKI destruction in, 169embryo development in, 161maturation promoting factor in, 99TR-B in, 376

Xenopus oocytes, studies in, 423Xeroderma pigmentosum (XP), 535, 537–538X-linked IAP (XIAP), 512–513, 762. See also

Inhibitor of apoptosis protein (IAP) familyXPA helicase, 535XPC-HHRAD23B protein, 535xR11 anti-apoptotic protein, 377XRCC1 protein, 539–541, 542XRCC4 protein, 547

YAP coregulatory factor, 26–27Yeast autophagy genes, 385. See also

Saccharomyces cerevisiae;Schizosaccharomyces pombe

Yeast cell cycle, 98Yeast mutants, 100, 101, 221Yeast RSC complex, 280–281Yeast SWI/SNF complex, 277–278Yin-yang principle, 715ySWI/SNF complex, 47

Zaidi, S. Kaleem, 15Zamamiri-Davis, Faith A., 635Zambetti, Gerard P., 635ZAP-70/Syk, 141Zinc finger motifs, 166. See also MOZ (monocytic

leukemia zinc finger protein); PLZF(promyelocytic leukemia zinc finger)


index [catalogimages.wiley.com]anti-apoptosis, ne-kb family and, 762–763.see also apoptosis...

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