CDK Regulation

Question 1

CDK phosphorylation

Answer 1

CDKs are kinases that phosphorylate targets but are also targets for regulatory phosphorylation themselves<br></br>1. Inhibitory<br></br>2. Stimulatory

Question 2

Stimulatory CDK phosphorylation

Answer 2

• Western blot of CDK2 shows that late G1 gets a second faster running band (that when treated with a phosphatase is removed)<br></br>- T-loop motif contains a Thr residue that is important for allowing full CDK activation<br></br>- Cyclin binding triggers T loop u

Question 3

T loop phosphorylation

Answer 3

• Promotes <u>active site access</u><br></br>- Further role in <u>substrate selection and positioning</u><br></br>- Phosphorylation of Thr is important in electrostatic positioning/alignment of the substrate<br></br>- Basic residue in substrate CDK binding motif interac

Question 4

Inhibitory Phosphorylation

Answer 4

NAME?

Question 5

GxGxxG motif

Answer 5

• Forms top of the binding pocket for ATP in the CDK2<br></br>- Phosphorylation then <b>influences</b> its activity/catalysis<br></br>- wee1 phosphorylates at T14/Y15 blocking substrate recruitment rather than inhibiting catalysis directly<br></br>- Conformation of resi

Question 6

Growth Arrest

Answer 6

• Wee1 important in growth arrest (eg. after exposure to DNA damaging agent)<br></br>- Damage induces wee1 expression, CDK phosphorylation, and a lack of Rb/E2F dissociation<br></br>- Also associated with normal growth control to finetune proliferation/ensure condi

Question 7

cdc25

Answer 7

NAME?

Question 8

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Answer 8

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Question 9

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Answer 9

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Question 10

Cyclin E/CDK2 in the cell cycle

Answer 10

• Essential for S phase entry<br></br>- <b>CDK2 required for cell cycle progression</b><br></br>Evidence:<br></br>1. Antibody microinjection: blocking of CDK2 via Abs prevents cell cycle progression<br></br>2. Inhibitors: inhibition of CDK causes G1 arrest<br></br>3. Expression o

Question 11

Cyclin/CDK complementation

Answer 11

• If cell cycle is perturbed enough, other cyclin/CDK complexes can fulfill the same roles<br></br>- Eg. cyclinE/A and CDK2/1 can perform same function in case of KO<br></br>-<i>Evidence supports this</i>

Question 12

Roscovitine

Answer 12

NAME?

Question 13

Bortezomib

Answer 13

NAME?

Question 14

PROTACS

Answer 14

NAME?

Question 15

CDK4/6 Inhibition

Answer 15

• More appropriate for selective targeting therapeutics<br></br>- Not as common as CDK1/2 in vivo

Question 16

Therapeutic Resistance

Answer 16

NAME?