Regulation of Cell NumberCell cycle and apoptosisRina SusilowatiDepartment of Histology and Cell Biology Faculty of Medicine Gadjah Mada University

Regulation of Cell NumberCell cycle and apoptosisKey Concepts Normal cell proliferation is modulated by cell cycle regulation.

Apoptosis is a normal self-destruction mechanism that eliminates damaged and potentially harmful cells.

Signaling systems permit proliferation and apoptosis to be coordinated within a population of cells.

Many of the classes of genes that are mutated to cause cancers are important components of the cell that directly or indirectly contribute to growth control and differentiation.

Junquiera Basic Histology (Courtesy of R Manelli-Oliveira, R Cabado, and G Machado-Santelli.)InterphaseProphaseMetaphaseAnaphaseEarly telophaseTelophase

Normal cell proliferation is modulated by cell cycle regulation.

Phases of the cell cycle in bone tissue. Junqueira Basic Histology

Observation of cell culture systeminhibitedNutrient deprivation

Contact inhibition

Exposure to inhibitors of RNA or protein synthesis

Complete development and differentiation

InducedGrowth factor signals

cell cycle

Extracellular factorTranscription factorGene ExpressionCell Cycle regulatorExtracellular signals activate or inhibit cell proliferationOncogeneTumor suppressor

Figure 8.3b The Biology of Cancer ( Garland Science 2007)Cell cycleNormal cell proliferation is modulated by cell cycle regulation. Cell differentiation

The Biology of Cancer ( Garland Science 2007)External regulationInternal regulationCell cycleNormal cell proliferation is modulated by cell cycle regulation.

Normal cell proliferation is modulated by cell cycle regulation. The Biology of Cancer ( Garland Science 2007)Cyclin

Normal cell proliferation is modulated by cell cycle regulation. The Biology of Cancer ( Garland Science 2007)Cyclin cyclin dependent kinase (CDK)CDK substratesTranscription factor gene expression

Histone chromatin condensation

Lamin lamin depolimerization

Normal cell proliferation is modulated by cell cycle regulation. The Biology of Cancer ( Garland Science 2007)Different combination of Cyclin and Cyclin-dependent kinase (CDK) are needed for each phase of cell cycle

Normal cell proliferation is modulated by cell cycle regulation. Different combination of Cyclin and Cyclin-dependent kinase (CDK) are needed for each phase of cell cycle

Normal cell proliferation is modulated by cell cycle regulation. Passage through the restriction point depends on activation of E2F Transcription factors

Normal cell proliferation is modulated by cell cycle regulation. Cyclin-kinase inhibitor contribute to cell-cycle control

Normal cell proliferation is modulated by cell cycle regulation. The Biology of Cancer ( Garland Science 2007)

What makes a cell decide to commit suicide?A normal physiological response to specific suicide signals or lack of survival signals

Apoptosis - Falling off - Programmed cell death cell suicide

Cytoplasmic shrinks without membrane rupture

To be engulfed by phagocytes

No spllilage, no inflammation

Apoptosis is a normal self-destruction mechanism

Caspases are central executioner of apoptosisCaspase: Cysteine Aspartate Specific ProteASEs

Apoptosis is a normal self-destruction mechanism

Mitochondrial pathwayApoptosis is a normal self-destruction mechanismInduced byDNA damageGrowth deprivation

Death receptor pathwayApoptosis is a normal self-destruction mechanism

Apoptosis is a normal self-destruction mechanismGranzyme pathway

Cell apoptosis can be induced either through caspase-2 or caspase-3 activationApoptosis is a normal self-destruction mechanism

Signaling systems permit proliferation and apoptosis to be coordinated within a population of cells

Signaling system alter the activation of cyclin-CDK inhibitorSignaling system coordinate proliferation and apoptosis

Signaling system coordinate proliferation and apoptosisGrowth factors are recognized by tyrosine kinase receptors

Signaling system coordinate proliferation and apoptosisGrowth factors are recognized by tyrosine kinase receptors

Normal cell proliferation is modulated by cell cycle regulation. The Biology of Cancer ( Garland Science 2007)

Thank you