nf2/merlin and neurofibromatosis
DESCRIPTION
NF2/Merlin and Neurofibromatosis. Maciej S. Tobola Biol 169 Cancer Biology March 30, 2004. Type II Neurofibromatosis. Autosomal dominant Nervous System Rare Two-Hit. Merlin in Adherens Junctions. No Adherens=No Contact Inhibition. McClatchey et al., 2003. Various KO’s. NF2 -/- Mouse - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/1.jpg)
NF2/Merlin and NF2/Merlin and NeurofibromatosisNeurofibromatosis
Maciej S. TobolaMaciej S. TobolaBiol 169 Cancer BiologyBiol 169 Cancer Biology
March 30, 2004March 30, 2004
![Page 2: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/2.jpg)
Type II NeurofibromatosisType II Neurofibromatosis
Autosomal dominantAutosomal dominant Nervous SystemNervous System RareRare Two-HitTwo-Hit
![Page 3: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/3.jpg)
Merlin in Adherens JunctionsMerlin in Adherens Junctions
No Adherens=No Contact InhibitionNo Adherens=No Contact Inhibition
McClatchey et al., 2003
![Page 4: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/4.jpg)
Various KO’sVarious KO’s
NF2NF2-/--/- Mouse Mouse• Dies QuicklyDies Quickly
Conditional NF2Conditional NF2-/--/- Mouse Mouse• Many SchwannomasMany Schwannomas
Drosophila Bluebox MutantDrosophila Bluebox Mutant• Overproliferation in wingOverproliferation in wing
![Page 5: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/5.jpg)
NF2NF2
Chromosome 22Chromosome 22
Nonsense & Frameshift mutationsNonsense & Frameshift mutations DeletionsDeletions
http://www.rzpd.de/cgi-bin/cards/carddisp?NF2
![Page 6: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/6.jpg)
MerlinMerlin
Protein 4.1 SuperfamilyProtein 4.1 Superfamily
Gutmann et al., 2002
![Page 7: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/7.jpg)
Merlin StructureMerlin Structure
Blue BoxBlue Box A-C Salt BridgeA-C Salt Bridge
Gutmann et al., 2002
![Page 8: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/8.jpg)
Activity in the CellActivity in the Cell
Open=InactiveOpen=Inactive Closed=Active Tumor SuppressorClosed=Active Tumor Suppressor
OpenClosed
Gutmann et al., 2002
![Page 9: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/9.jpg)
Activity in the CellActivity in the Cell
McClatchey et al., 2003
![Page 10: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/10.jpg)
NeurofibromatosisNeurofibromatosis
No Rac1 InhibitionNo Rac1 InhibitionMerlin PhoshorylationMerlin PhoshorylationIncreased ProliferationIncreased Proliferation
McClatchey et al., 2003
![Page 11: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/11.jpg)
Remember This?Remember This?
No Adherens=No Contact InhibitionNo Adherens=No Contact Inhibition
McClatchey et al., 2003
![Page 12: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/12.jpg)
Cancer RecipeCancer Recipe
Increased Proliferation +Increased Proliferation +
Loss of Contact Inhibition =Loss of Contact Inhibition =
Neurofibromatosis Type II
http://www.neurofibromatosis.org/what_is_nf/nf2_technical.htm
![Page 13: NF2/Merlin and Neurofibromatosis](https://reader036.vdocuments.us/reader036/viewer/2022082819/56813ff6550346895dab1bf3/html5/thumbnails/13.jpg)
Treatment OptionsTreatment Options
SurgerySurgery• Location complicationsLocation complications
Focused Radiation TherapyFocused Radiation Therapy
Sign LanguageSign Language