Cell Cycle & Apoptosis

Regulation of Cell Number Cell cycle and apoptosis Rina Susilowati Department of Histology and Cell Biology Faculty of Medicine Gadjah Mada University

Regulation of Cell Number Cell cycle and apoptosis Key Concepts 

Normal cell proliferation is modulated by cell cycle regulation.

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

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

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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.

Interphase

Prophase Metaphase

Anaphase Early telophase Telophase

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

Normal cell proliferation is modulated by cell cycle regulation.

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

Observation of cell culture system cell cycle

• Induced

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inhibited  Nutrient deprivation 

Contact inhibition

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Exposure to inhibitors of RNA or protein synthesis

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Complete development and differentiation

• Growth factor signals

Extracellular signals activate or inhibit cell proliferation

Extracellular factor

Gene Expression

Transcription factor

Oncogene Tumor suppressor

Cell Cycle regulator

Normal cell proliferation is modulated by cell cycle regulation.

 Cell differentiation

Cell cycle

Figure 8.3b The Biology of Cancer (© Garland Science 2007)

Normal cell proliferation is modulated by cell cycle regulation.

Internal regulation

External regulation

Cell cycle

The Biology of Cancer (© Garland Science 2007)

Normal cell proliferation is modulated by cell cycle regulation.

Cyclin

The Biology of Cancer (© Garland Science 2007)

Normal cell proliferation is modulated by cell cycle regulation.

Cyclin – cyclin dependent kinase (CDK) CDK substrates  Transcription factor  gene expression

The Biology of Cancer (© Garland Science 2007)

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Histone  chromatin condensation

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Lamin  lamin depolimerization

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

The Biology of Cancer (© Garland Science 2007)

Normal cell proliferation is modulated by cell cycle regulation. Different combination of Cyclin and Cyclindependent 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

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Apoptosis - Falling off Programmed cell death – cell suicide

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Cytoplasmic shrinks without membrane rupture

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To be engulfed by phagocytes

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No spllilage, no inflammation

Apoptosis is a normal self-destruction mechanism

Apoptosis is a normal self-destruction mechanism

Caspases are central executioner of apoptosis 

Caspase: Cysteine Aspartate Specific ProteASEs

Apoptosis is a normal self-destruction mechanism

Mitochondrial pathway Induced by DNA damage Growth deprivation

Apoptosis is a normal self-destruction mechanism

Death receptor pathway

Apoptosis is a normal self-destruction mechanism

Granzyme pathway

Apoptosis is a normal self-destruction mechanism

Cell apoptosis can be induced either through caspase-2 or caspase-3 activation

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

Signaling system coordinate proliferation and apoptosis

Signaling system alter the activation of cyclinCDK inhibitor

Signaling system coordinate proliferation and apoptosis

Growth factors are recognized by tyrosine kinase receptors

Signaling system coordinate proliferation and apoptosis

Growth 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