Cell Cycle 4

Question 1

What are the other names of:

a) Cip
b) Kip1
c) Kip2

Answer 1

a) p21
b) p27
c) p57

Question 2

How were p21, p27 and p57 discovered?

Answer 2

Yeast 2 hybrid looking for proteins that associated with cdks

Question 3

What can p57 mutations cause?

Answer 3

Beckworth Weidemenn syndrome

Overgrowth of certain areas of body in development - often tongue

Question 4

Relative levels of (a) and (b) control exit from G0 to G1?

Answer 4

p27 and cyclin D

Question 5

Why are p21 and p27 rarely mutated in cancer?

Answer 5

The inactive form stabilises cdk4/cyclin D complex and allows the complex to enter the nucleus

Question 6

Where does cdk2/cyclinE phosporylate p27?

Answer 6

T187 - leads to degradation of unbound p27 by polyubiquitination

Question 7

What is recruited when p27 is phosphorylated?

Answer 7

Fbox, which then recruits factors that ubiquitinates p27 e.g. Skp1 - the E3 domain of E1-E2-E3
Then degraded by the proteosome
All components often mutated in cancer

Question 8

What keeps the cell cycle moving in the same direction?

Answer 8

Each new cyclin causes the expression of the next. Once the next cyclin is produced it, the cdk-cyclin complex phosphorylates the previous cyclin, tagging it for degradation.

Question 9

In vivo what do cdk inhibitors inhibit?

Answer 9

cdk4/6 and 2 - because inhibitors are degraded after this