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
Regulation of Cell Number
Cell cycle and apoptosis
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.
Junquiera Basic Histology (Courtesy of R Manelli-Oliveira, R Cabado, and G Machado-Santelli.) Interphase Prophase Metaphase Anaphase Early telophase Telophase
Normal cell proliferation is modulated by cell cycle regulation.
inhibitedinhibited
Nutrient deprivationNutrient deprivation
Contact inhibitionContact inhibition
Exposure to Exposure to inhibitors of RNA or inhibitors of RNA or protein synthesis protein synthesis Complete Complete development and development and differentiation differentiation
•
Induced
Induced
•
Growth factor signals
Growth factor signals
Observation of cell culture system
Observation of cell culture system
cell cycle
Extracellular factor
Transcription factor
Gene Expression
Cell Cycle
Cell Cycle
regulator
regulator
Extracellular signals
Extracellular signals
activate or inhibit cell
activate or inhibit cell
proliferation
proliferation
Oncogene
Oncogene
Tumor suppressor
Tumor suppressor
Figure 8.3b The Biology of Cancer (© Garland Science 2007)
Cell
cycle
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
Cell
The Biology of Cancer (© Garland Science 2007) External regulation Internal regulation
Cell
cycle
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
The Biology of Cancer (© Garland Science 2007)
Normal 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 – cyclin dependent kinase (CDK)
CDK substrates Transcription factor gene expression Histone chromatin condensation Lamin lamin depolimerization
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
The Biology of Cancer (© Garland Science 2007)
Different combination
Different combination
of Cyclin and
of Cyclin and
Cyclin-dependent kinase
dependent kinase
(CDK) are needed for
(CDK) are needed for
each phase of cell
each phase of cell
cycle
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
Different combination
Different combination
of Cyclin and
of Cyclin and
Cyclin-dependent kinase
dependent kinase
(CDK) are needed for
(CDK) are needed for
each phase of cell
each phase of cell
cycle
Normal cell proliferation is modulated by cell cycle regulation.
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.
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
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
apoptosis
Caspase:
Cysteine Aspartate Specific ProteASEs
Apoptosis is a normal self-destruction mechanism
Mitochondrial pathway
Apoptosis is a normal self-destruction mechanism
Apoptosis is a normal self-destruction mechanism
Induced by
DNA damage
Death receptor pathway
Apoptosis is a normal self-destruction mechanism
Apoptosis is a normal self-destruction mechanism
Apoptosis is a normal self-destruction mechanism
Cell apoptosis can be induced either through
caspase-2 or caspase-3 activation
Apoptosis is a normal self-destruction mechanism
Signaling systems permit proliferation and
Signaling systems permit proliferation and
apoptosis to be coordinated within a population
apoptosis to be coordinated within a population
of cells
Signaling system alter the activation of
Signaling system alter the activation of
cyclin-CDK inhibitor
CDK inhibitor
Signaling system coordinate proliferation and apoptosis
Signaling system coordinate proliferation and apoptosis
Signaling system coordinate proliferation and apoptosis
Growth factors are recognized by tyrosine
Growth factors are recognized by tyrosine
kinase receptors
Signaling system coordinate proliferation and apoptosis
Signaling system coordinate proliferation and apoptosis
Growth factors are recognized by tyrosine
Growth factors are recognized by tyrosine
kinase receptors
Normal cell proliferation is modulated by cell cycle regulation.
Normal cell proliferation is modulated by cell cycle regulation.
