CFM 2: Cell Cycle
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Most cells are in which phase of the cell cycle?
Difference between G1 phase, G0 phase, and post-mitotic cells?
- G1: average dividing cells
- G0: quiescent cells (not dividing, but can be stimulated to enter cell cycle)
- Post-mitotic: incapable of cell division (e.g. mature neurons)
Where in the cell cycle is the R checkpoint?
Just before G1/S checkpoint
What is the main purpose of the R point in human cell cycle?
- Checks growth conditions
- Before R point, checking for sufficient growth factors
- After R point, growth factors do not matter; the cell is committed to replicating
What happens if a cell does not receive enough growth factors before the R point?
Stays in G0 phase
CDKs are (active/inactive) on their own
CDKs are activated by ______
2 different ways p53 acts as a tumor suppressor and protects us from cancer?
- Induces apoptosis
- Stops cell cycle by inducing transcription of p21, which is a Cdk inhibitor protein
Cdk inhibitor protein; transcription induced by p53
p53/p21 pathway in stopping cell cycle
- DNA damage to UV rays
- ATM/ATR repair pathway activated
- Ultimately activating p53
- p53 induces p21 transcription
- p21 inhibits G1/S-Cdk and S-Cdk
Phosphorylates CDK1 to inhibit CDK1 activity during S phase
Phosphatase that dephosphorylates Cdk1 to allow progression from G2 to M
G1 (R point) cyclin and Cdk
Wnt inhibits APC inhibits B-catenin stimulates cyclin D transcription
Rb and its effects on cell cycle
- Rb binds and inhibits E2F, a transcription factor that stimulates transcription of Cyclin E
- E2F is activated when Cyclin D-Cdk4 phosphorylates Rb, releasing E2F
How does Cyclin D activation lead to Cyclin E activation?
- Cyclin D phosphorylates Rb, releasing E2F (to which unphosphorylated Rb is bound and inhibiting)
- E2F promotes transcription of Cyclin E
How do cyclins/CDKs ensure just one round of DNA replication per cell cycle? Which cyclin/CDK complex does this?
Cyclin E/Cdk2 phosphorylates pre-replicative complexes on DNA when cells enter S phase, degrading them
Two major ubiquitin ligase complexes in cell cycle control
- APC (anaphase promoting complex)
- SCF complex
- Kind of ubiquitin ligase
- Has F-box, which is interchangeable and specific to target proteins
- F-boxes mostly interact with phosphorylated proteins to degrade them; many of the targets are phosphorylated by cyclin/CDKs, which allows substrates to be degraded during specific phases of the cell cycle
2 functions of Anaphase Promoting Complex (APC)
- 1. ubiquitin ligase that ubiquitinates Cyclin B (G2/M cyclin)
- 2. Allow chromosome segregation by ubiquitinating securin (which inhibits separase), activating separase, which unglues cohesin complexes allowing chromosomes to separate
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