Cell Cycle II Flashcards
What is cdk1?
It’s a cell division cycle protein and is a ser/thr kinase. It’s called cdc2 in fission yeast. It’s cdc28 in budding yeast. In humans, it’s cdc2.
What is MPF and how is it involved in regulating the cell cycle?
MPF is CDK1 and cyclin B. It is mitosis promoting factor which is released in the cytoplasm upon start of mitosis. Cyclin is rapidly degraded by the end of mitosis.
What controls the cell cycle progression?
Variety of cdk/cyclin complexes have unique substrate specificity. Phosphorylation of different substrates induces different cell cycle transitions.
How is cyclin degraded?
Cyclin is modified by covalent coupling to ubiquitin. Polyuniquitylation means many are added and it triggers the protein for destruction by the proteasome. This also inactivates cdk1 cuz of complex of cdk1/cyclin b.
What is the ubiquitin ligase for cyclin b?
Anaphase promoting complex (APC)
What experiments proved that cyclin synthesis and degradation drives the cell cycle?
- Fertilized egg triggers cell cycle. When add RNAse, degrade cyclin RNA. This tells you there’s an important RNA for cell cycle since this addition keeps it in interphase.
- Add RNAse and nondegradable cyclin B RNA. This makes the cell cycle stick in m phase. This tell us presence and degradation of cyclin is critical for cell cycle progression.
How can you tell that cell cycle transitions are switch like?
Mitosis, MPF activity levels, and cyclin protein levels are all on and off at the same time. Cyclin degradation acts as a switch for mitosis to turn off.
What mutations stop cell division in fission yeast? What makes them divide prematurely? What’s an activator or inhibitor of this same protein?
Cdc2 mutant stops cell division. Cdc2 dominant makes the cell divide prematurely. So cdc2 is necessary for cell division but only at certain times is it effective in the normal sense.
Cdc25 is a phosphatase that gets rid of phosphate groups that are inhibitory (acts as a cdc2 activator).
Wee1 is a kinase that is a cdc2 inhibitor by phosphorylation at inhibitory AA.
What happens in a cdc25 mutant? Wee1 mutant?
No cell division in cdc25 mutant cuz it’s supposed to activate cdc2.
Early cell division in wee1 mutant.
What are the positive and negative feedback loops in the progression of cdk1/cyclin activation?
Negative feedback: cdk inhibits and degrades wee1
Positive feedback: cdk phosphorylates cdc25 and increases its activity.
What are the substrates for cdks involved in?
Translation, actin and cell polarity, chromatin structure, DNA replication, nuclear transport, spindle, kinetichore, cytokinesis.
What’s an example of a cdk substrate in mammals?
Nuclear envelope. It breaks down at G2➡️M. The breakdown allows spindles to attach to the chromosomes. The nuclear lamina is phosphorylated at this time by cdk1/cyclin B.
What are cell cycle checkpoints? Examples?
Timing of steps of cell cycle ensure transitions Are irreversible. Checkpoints make sure each process is complete before the next begins or otherwise halt the cell cycle.
Examples: G2 checkpoint for DNA all replicated and not damaged in order to enter M. M check point would be before anaphase (make sure all chromosomes are properly attached to mitotic spindle). G1 checkpoint would be to make sure environment is favorable for replication and segregation.
What’s the progression of steps in DNA damage checkpoint?
DNA damage activates ATM kinase, which phosphorylates p53, which is a TF for p21, which is an inhibitor of cdk1 for the G1/S phase transition, which stops the cell cycle.
What’s the significance of p53?
It’s a tumor suppressor gene. If p53 mutant, then no induction of p21 (cdk inhibitor) and cell cycle proceeds. This can lead to development of a tumor.
