Lecture 10

Question 1

Cell Cycle Checkpoints

Answer 1

• Checkpoints ensure condition suitable for division
• Mediated by controlled activity of cyclin-dependent kinases(Cdks)
• Phosphorylate target proteins for cell cycle to progree -> require cyclins

Question 2

Cyclin-cdk

Answer 2

• Cdks present throughout all cell cycle stages
• Cyclins made and broken down at different cell cycle stages
• Cyclin-Cdk combination controls which target proteins are phosphorylated
• G1/S and S-Cdk target DNA helices
• M-cdk target lamins and microtubule-associated proteins
• One Cdk may work with multiple cyclins, but cyclins only work at one stage
• Polyubiquiantion marks cyclins for degradation -> Cdk not active
• APC/C and Cdc20 act on E3 ubiquitin ligase

Question 3

Cdk-Activating Kinase

Answer 3

• Cyclin absolutely required for Cdk activity by exposing T-loop
• CAK can phosphorylate Cdk to activate
• PP2A remove phosphorylation -> same target as Cyclin-Cdks -> involve in feedback loop with Cyclin-Cdks

Question 4

Cdk inhibitor proteins(CKI)

Answer 4

• CKI bind cyclin-cdk to inactivate
• eg. p27 and p21

Question 5

Inhibitory phosphorylation

Answer 5

• Inhibitory phosphorylation at different site from activating phosphate
• Wee1 kinase adds inhibitory phosphorylation
• Cdc25 remove inhibitory phosphorylation -> needs to be phosphorylated to be active

Question 6

Cells retained in G1 by Rb

Answer 6

• E2F transcription factor required for S phase gene expression
• Rb binds and inhibits E2F
• Rb inhibited by phosphorylation

Question 7

Myc

Answer 7

• Mitogens trigger production of Myc -> key transcription factor

Question 8

p53

Answer 8

• DNA damage induces p53 -> activates p21 expression -> p21 is CKI that inhibits G1/S-Cdk and S-Cdk