THE CELL CYCLE 4 Flashcards
what does the retinoblastoma protein do?
considered a handbrake on passing the restriction point and cell cycle entry.
what and how was the first tumour suppressor gene discovered?
first tumour suppressor gene was retinoblastoma due to previous knowledge on its chromosomal location.
where is Rb found?
in the nucleus of all mammalian cells.
what does Rb play a central role in? Why?
regulating progression past the restriction point. due to its ability to bind to and inactivate the transcriptional activity of
E2F, a transcription factor
what happens as Rb progresses in the cell cycle?
it gets progressively more and more phosphorylated.
what does Rb regulate?
the activity of E2F, a transcription factor required for synthesis of gene products necessary to pass start.
what is phosphorylated Rb not capable of doing anymore?
inhibiting transcriptional activity of E2F
when does Rb release its hold on E2F after phosphorylation? with what
during mid G1 with cyclin dependent kinases.
what is E2F in a family of?
transcription factors
what does induction of myc, cyclin D and cyclin E by E2F suggest?
that a positive feedforward loop exists which explosively drives the synthesis of cyclins in mid to late G1 and pass the restriction point.
what happens late in S-phase with E2F?
it becomes inactivated due to CDK/Cyclin activity, aka loses DNA binding capability.
true or false - Rb is not found in mutant forms in tumors
false
what does mutant pRb do in cells?
fails to put a brake on the cell cycle.
what type of gene is Rb referred to as?
tumor suppressor gene.
what do some viruses do to pRb leading to cancer?
Multiple tumor causing viruses inactivate pRb by encoding proteins that
bind to pRb and displace E2F
why do viruses try to drive cells into the cell cycle?
to try enter the nucleus and transcribe their own genes.
how does a cell exit the cell cycle?
when it receives a signal from growth inhibitory factors eg Transforming Growth Factor.
give 2 proteins that can arrest the cell cycle predominantly in G1?
INK4 and CIP/KIP protein families.
how does CIP/KIP activate?
appears
that the CIP/KIPs can act
right at the restriction point
by inactivating the
CDK4/cyclinD complex
responsible for inactivating
Rb and releasing E2F, and
can also act downstream of
this
what does INK4 act on ?
only on the CDK4/cyclin D complexes
