Cell Cycle Flashcards
(39 cards)
What are the phases of the cell cycle?
G0, G1, S, G2, M
What happens in G1 phase?
Cell growth and preparation for DNA synthesis
What happens in S phase?
DNA synthesis
What happens in G2 phase?
Cell growth and preparation for mitosis
What happens in M phase?
Mitosis
What are cyclins and CDKs and how do they work together?
- Cyclin = protein expression oscillates over cell cycle
- Cyclin dependent kinase = stable expression
- Cyclin proteins bind to cyclin dependent kinases
- Each have low activity individually, but when bound CDK will phosphorylate
What cyclin-Cdk combos are present in G1?
Cdk4-cyclin D and Cdk6-cyclinD
What cyclin-Cdk combo is present in S and G2?
Cdk2-cyclin A
What cyclin-Cdk combo helps with the G1/S transition?
Cdk2-cyclin E
What cyclin-Cdk combo is present in G2 and M?
Cdk1-cyclin B
How is CDK/Cyclin activity regulated?
Availability of corresponding proteins:
- regulated expression of cyclin genes
- regulated degradation of cyclin genes
Activity of complex depends on:
- CKI activity
- Inhibitory/activating phosphorylations of Cdk/cyclin
Describe the temporal expression of cyclin and Cdk genes.
Cdk = constant
Cyclin = oscillates across different phases of the cell cycle
What is the pathway for the cyclic degradation of cyclins?
For M-cyclin, APC/C (an E3 ubiquitin ligase) controls proteolysis. Other cyclins have other E3 ligases (F-box proteins):
- Activation of APC/C:
- Cdc20 activating subunit binds inactive APC/C - Ubiquitylation of cyclin:
- E1, E2, and APC/C ubiquitylate the cyclin
- polyubiquitin chain is added to K residue - Degradation in proteasome
What determines cyclin stability?
Cyclin ubiquitylation
How are inhibitory and activating phosphorylation involved in cell cycle progression?
- Cyclin and Cdk bind, forming an inactive complex
- Protein complexes add inhibitory and activating phosphates
- Inhibitory phosphate trumps activating - Activating protein phosphatase removes the inhibitory phosphatase
- Active cyclin-Cdk complex
What are the 4 mechanisms of Cdk activity regulation?
- Availability of cyclins
- Activating phosphorylation
- Inhibitory phosphorylation
- Association with Cdk Inhibitors (CKIs)
How does cyclin activation progress through the cell cycle?
S: Cyclin A-Cdk2
G2: Cyclin A-Cdk1, cyclin B-Cdk1
M:
G1: Cyclin D-Cdk4, cyclin D-Cdk6, cyclin E-Cdk2
What is a CKI?
Cyclin inhibitor protein: inhibits the active cyclin-Cdk complex (ex: p27)
How (temporally and mechanistically) is CKI proteolysis regulated?
Cyclically regulated through the ubiquitylation pathway
- CKI phosphorylated by a kinase
- Active SCF (F-box protein) complex (an E3 ubiquitin ligase) controls proteolysis: ubiquitylation of CKI by E1-E3.
- Degradation in proteasome
What Cdk-cyclin complexes are inhibited by the INK4 family of CKIs?
G1 phase: Cdk2,6-cyclinD
What Cdk-cyclin complexes are inhibited by the CIP/KIP family of CKIs?
G1 phase: Cdk2-cyclin E
S phase: Cdk2-cyclin A
G2 phase: Cdk2-cyclin A
M phase: Cdk1-cyclin B
Where in the cell cycle are the checkpoints? What is necessary to pass the checkpoint?
G1 checkpoint (major checkpoint) requires:
- cell size
- nutrient availability
- growth factors present
- no DNA damage
S phase: check for DNA damage
G2 checkpoint requires:
- cell size
- successful chromosome replication (no DNA damage or unreplicated DNA)
Metaphase checkpoint requires:
- all chromosomes attached to mitotic spindle
What are the downstream mechanisms by which cyclin-Cdk activity determine cell cycle position?
- Change gene expression and activate cell cycle stage specific transcription
- Modify activity of existing proteins, exerting direct control over cell cycle specific processes
What signals regulate exit from G0 and entry into the cell cycle?
- Growth signals (+ or -) from nearby cells
- TGFB signalling pathway
- Differentiaiton signals
- Cell-cell ECM contacts
- DNA damage