Regulation of the Cell Cycle ! Biological Sciencess !!

Regulation of the Cell Cycle

1. Cell cycle is driven by specific chemical signals in the cytoplasm.

2. M phase cells that are fused with any other phase cell, the latter cell will enter
mitosis.

3. Cell cycle control system triggers and coordinates key events in the cell cycle.

4. Cell cycle checkpoints act as stop and go signals. Three major checkpoints found in
G1
, G2
, and M phases.

(a) G1 is critical checkpoint. If cells make it past G1, the entire cell cycle is completed.
(b) Non-dividing cells are in G0 state.

5. Fluctuations in cell cycle control molecules abundance and activity control cell cycle.

• Protein kinases are activated by cyclin proteins.
• Activity of protein kinase is correlated with concentration of specific cyclin (cyclin
dependent kinase or “Cdk”).
6. MPF (maturation promoting factor) was first Cdk described.
• Cyclin level rises during interphase.
• At G2, enough active MPF (cyclin + Cdk) is present to promote mitosis.
• Numerous phosphorylation events that cause nuclear envelope to fragment
and activate other enzymes.
• Cyclin is broken down by proteolytic cleavage (MPF inactive) and Cdk is recycled.
• Proteolysis also drives M-phase past anaphase by breaking down proteins that
hold sister chromatids together.

7. Internal and External Cues Regulate Cell Cycle Internal signal delays start of
anaphase (separation of chromosomes) until all kinetochores are attached to spindle
fibers.

• Anaphase promoting complex (APC) is kept in inactive state by proteins associated
with kinetochores.
• Signal ceases when all kinetochores are attached.

8. Growth factors are external signals that stimulate cells to divide.

• Platelet derived growth factor (PDGF) is required for division of fibroblasts.
• PDGF binds to tyrosine kinase receptors on surface of cells and triggers signal
transduction pathway.

9. Density dependent inhibition describes phenomenon whereby cells stop growing
after reaching a certain density. Growth is limited by availability of growth factor.

10. Cancer Cells Have Escaped Cell Cycle Controls

• Cancer cells do not exhibit density dependent inhibition.
• Cancer cells do not stop growing when growth factor is depleted.
• Cancer cells stop at random points in cell cycle (not checkpoints).
• Some cancer cell lines are immortal and can divide indefinitely given the right
ingredients.e.g. HeLa cells.
• p53 gene mutations in tumor suppressor genes (e.g. p53) result in cancer functional
p53 aids cell in checkpoint control at G1 and G2

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