Cell cycle

Question 0

Rb structure?

Answer 0

3 domains:

1. RBN
2. RBC
3. Pocket domain with A and B subdomain; has LXCXE binding site (condensin binds here; mutation here may –> noncondensed chromatin)

Question 1

Increase Rb? mechanisms?

Answer 1

Stop cell progression

1. bind E2F (inactivate)
2. bind SKP-2 (inactivate)
3. bind APC which then ubiquinates and degrades SKP2

Question 2

Increased SKP2?

Answer 2

Cell cycle progression

ubiquinates and destroys p27

Question 3

Increased APC?

Answer 3

Depends

1. binds Rb –> ubiq destroy SKP2 –> stop
2. binds cdc20 –> ubiq securin –> activates separase –> cohesin degrad and cell progression

Question 4

Increase E2F

Answer 4

Cell cycle progression (S entry from G1)

Question 5

G1 cdK?

Answer 5

cyclin D + CDK 4/6

Question 6

MPF?

Answer 6

M-CDK

cyclin B + cdc2 (aka CDK-1)

Question 7

cdc20 fxn?

Answer 7

bound to Mad2 (bound to unbound kinetochores)
released when kinetochore bound
free cdc20 binds APC, which ubiquitinates securin –> release of separase

Question 8

increase p53 impact on cell progression? LOF mutation?

Answer 8

stops cell progression

LOF mutation –> cell progression

Question 9

CKI examples?

Answer 9

p21/p27

Question 10

Increase p21/p27?

Answer 10

Binds G1/S-CDK and S-CDK –> cell arrest

Question 11

Increase c-myc?

Answer 11

Proto-oncogene
burkitt’s lymphoma- c-myc translocation
c-myc increases expression of cyclin D, SCF, E2F

Question 12

Increase Ras

Answer 12

cell cycle progression

activated after resolving damage –> increased expression of protooncogenes like c-myc

Question 13

Increase SCF?

Answer 13

Cell progression

degrades p21/p27