3. Cell cycle phases
• Checkpoints control transitions between phases
of cell cycle. This process is regulated by
cyclins, cyclin-dependent kinases (CDKs), and
tumor suppressors.
• M phase (shortest phase of the cell cycle)
includes mitosis (prophase, prometaphase,
metaphase, anaphase, telophase) and cytokinesis
(cytoplasm splits in two).
• G1 is of variable duration
3
5. Cyclin-dependent kinase (CDK)
• A type of inactive kinase that must be activated to enable the transition from
one phase of the cell cycle to the next
• Present throughout the entire cell cycle
• Activated via binding of cyclins to form cyclin-CDK complexes
• Inhibited by cyclin-dependent kinase inhibitor proteins (CDKIs) if any errors in
the genome are detected
9. Regulation
• Cyclin D/Cdk4 complex
• A regulatory protein complex that initiates DNA replication by inactivating pRb
• Cyclin D/CDK4 complex phosphorylates pRb → pRb inactivation → release of previously
bound transcription factor E2F → transcription of genes that are required for DNA
replication
10. Regulation
• p53 tumor suppressor
• A protein that inhibits DNA replication by activating pRb and initiates apoptosis of the cells with
irreparable DNA damage
• DNA damage → activation of protein kinases → phosphorylation of p53 → activation
of p21 → inhibition of Cdks → inhibition of Cdk
mediated phosphorylation of pRb → pRb activation and binding of transcription
factor E2F → cell arrest in the G1 phase (no entry into the S phase)
• Activation of the p27 protein (a phosphoprotein that prevents cell cycle progression by
inhibiting cyclin/cyclin-dependent kinase complexes) leads to the same sequence of events.
• Present in every cell but undergoes continuous ubiquitylation and degradation
• Phosphorylated p53 can no longer be ubiquitinylated and degraded, leaving it free to act as
a transcription factor.
• Proapoptotic active proteins of the Bcl-2 family such as Bax and Bak
