regulation of cell cycle (13) Flashcards
when does the commitment to proceed into mitosis occur?
shortly before the beginning of S phase
where are the two other checkpoints in the cell cycle?
entry into mitosis (between G2 and M)
transition from metaphase to anaphase (during M)
what is the regulatory subunit that must be combined with the cdk to make it active?
a cyclin
describe the concentration flow of cyclin and the kinase subunits during the cell cycle
The concentration of the cyclin subunit of a mitotic cdk increases gradually during the cell cycle then decreases suddenly
-the kinase concentration stays constant
why is there a “lag” between the increase in cyclin activity and the activation of cdk? (3 factors/steps)
- The cyclin subunit must be synthesized and must bind to the kinase
- The catalytic subunit is phorphorylated. 1 phosphate is needed for CDK activity, the other inhibits the cdk activity
- A phosphatase removes the inhibitory phosphate, activating the cdk
what is the name of the cdk inhibitor kinsase?
wee1
what is the name of the cdk activating kinase?
Cak
what is the final step in cdk activation?
removal of the inhibitory phosphate by a protein phosphatase starts a positive feedback loop. Activity of a few molecules of the cdk as a protein kinase stimulates the phosphatase to make more active cdk molecules
how do you inactivate cdk?
- Cyclin subunit is ubiquitylated by an E3 ubiquitin ligase, targeting the cyclin subunit for the proteolytic destruction by the proteosome
- The activating phosphate is removed from the kinase subunit
how many kinetchores need to be attached for the E3 ligase activation?
all of them
will not occur if even one isn’t attached
what is the APC?
a ubiquitin E3 ligase, targeting proteins for desctruction
what activates the APC?
tension on all the kinetochores
what are the two main proteins that p53 activates transcription for?
p27 and p21
what is cisplatin? why and how does it work?
it is a DNA damaging agent
why it works in brca cancers:
-If you damage the dna enough, and you cant fix it—you can induce apoptosis
in addition to DNA damaging agents, what is another molecule that can be used in brca cancers?
dna repair inhibitors
ex. PARP inhibitors