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.

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.

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

inhibited
Nutrient deprivation

Contact inhibition

Exposure to
inhibitors of RNA or
protein synthesis

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)

Histone
chromatin
condensation

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

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

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