10 - Regulation of Proliferation II Flashcards
What will p53 do if everything in cell is not okay to continue the cell cycle?
will induce cell cycle arrest to fix whatever needs to be fixed
What is the status of CDKs by itself?
inactive , off
What will happen to CDK when the cell begins to produce cyclins?
cyclin = binds to CDK »_space;> conformational change = active form
How are CDKs promiscuous?
can bind to different cyclins
What are the 2 categories of cyclins?
S-phase (D and E cyclins) | Mitotic (A and B cyclins)
How can a cell jump to G1 from G0?
Rb needs to be turned off to release E2F
What are allosteric enzymes?
shape-dependent enzymes
Where was p53 discovered?
virally induced cancers
About how many cancers involve a mutation in p53?
50%
How many mutations in p53 is needed for the cell to lose control?
one = proto-oncogene
What do viral proteins predominantly bind to on the p53 gene?
DNA-binding domain
What are the viruses preventing by binding onto the p53 binding domain?
prevents p53 from binding onto DNA = inhibits the DNA binding mechanism of host-cell transcription
What is the structure of p53? How is this a problem?
homotetramer | if one part is mutated = it is automatically dysfunctional as they won’t be able to bind stably or at all
What are the 3 effects of p53 on cellular response when it is working?
cell-cycle arrest | apoptosis | prevents angiogenesis
What other nucleic molecule does p53 also protect?
mitochondrial DNA
What is Bax?
induces apoptosis
What is p21?
one of the inhibitors p53 turns on | arrests cell cycle, evaluates if cell can be saved, if mutations can be fixed
If the cell cannot be saved, what does p21 do?
induces Bax »_space;> apoptosis
In p53+/- mutation, how is p53 still working when one copy is mutated and shouldn’t work?
still has one other functional copy
What can inhibit p53? (antagonist against p53)
MDM2
What is MDM2?
inhibits p53, regulates its activity | made with help from p53
What is the p53-MDM2 feedback loop?
MDM2 binds to p53 »_space;> MDM2 ubiquitinylates p53 for degradation
How many proteins of MDM2 are needed to act on p53? Why?
4 since p53 is a tetramer
What is benzopyrene and why is it important?
chemical in cigarettes that can react with DNA when broken down and become reactive
Where do most mutations of proteins seem to occur?
DNA binding domain
What are the 2 types of hotspots for mutations?
within DNA and can be tissue-specific | reasons are unknown
What is the 4-step program to transformation?
eliminate Rb | disable p53 | activate telomerase | acquire growth-promoting mutation or activity
