Cell Cycle, Cancer, and Cell Death

Question 1

What are stimuli that trigger active growth cycle or G0 stage? (5)

Answer 1

1. growth factor receptors
2. monitors of genome intergrity
3. TGF-β receptors
4. integrins
5. monitors of cell metabolism

Question 2

When will the amount of DNA in a cell be the least? the most?

Answer 2

• least: G1 phase
• most: after S phase, either G2 or M phases

Question 3

What cyclins are a/w what cell cycle phases?

Answer 3

• G1: C, D1-3, E1-2, F, G
• S: A
• G2/M: B1-2

(cyclin H is constitutive)

Question 4

What CDKs pair with what cyclins?

Answer 4

• CDK4/CDK6 = cyclin D
• CDK2 = cyclin E and A
• CDK1 = cyclin B

Question 5

What protein is essential to CDK’s for cyclin bonding?

Answer 5

PSTAIRE α-helix

Question 6

How is CDK activiated?

Answer 6

• cyclin-CDK complex
• CDK must be phosphorylated on one certain site, but desphosphorylated on other two sites
• protein phosphatase CDC25 dephosphorylates CDK’s

Question 7

What are positive regulators of cell cycle? (4ish)

Answer 7

• CDK1
• CDK2
• CDK4/CDK6
• CDC25 A, B, and C phosphatases

Question 8

How is the cell cycle negatively regulated?

Answer 8

• inactivation by inhibitor binding and phosphorylation interference
• when INK4 binds, twisting of CDK upper lobe blocks cyclin binding or interferes with ATP hydrolysis
• when p27 or p21 binds, a loop insinuates into the upper lobe of CDK and blocks ATP binding

Question 9

What are negative regulators of cell cycle? (7 lol)

Answer 9

• p21 (CKI)
• p27 (CKI)
• p57 (CKI)
• p15 (INK4)
• p16 (INK4)
• p18 (INK4)
• p19 (INK4)

Question 10

____ proteins receive their signals from catalytic receptors that have been activated by their ligand, the overall effects of ____ (same word) signaling often involve induction of cell proliferation

Answer 10

Ras

Question 11

What is the restriction point of cell cycle entry and progression?

Answer 11

cyclin D - CDK4/6 complex activating of cyclin E and binding of cyclin E to CDK2

Question 12

Describe the G1/S transition:

Answer 12

• E-CDK2 increases pRb hyperphosphorylation
• liberated E2F transcription factors increase transcription of cyclin E and E2F1 genes
• increase of cyclin E and E-CDK2 complexes
• increase in pRb phosphorylation
• E2F1 drives its own expression

Question 13

Describe G2/M transition:

Answer 13

• B-CDK1 activated and maintained by CDC25 and translocates to nucleus to initiate spindle assembly
• anaphase activated, promoting complex (APC) destroy CDK1, freeing cyclin B for degradation

Question 14

When do the 3 cell cycle checkpoints occur?

Answer 14

• G1 phase
• S phase
• G2 phase

Question 15

Describe G1 checkpoint in terms of DNA damage and its 2 pathways:

Answer 15

• pathways are parallel, occur after DNA damage
• slower: stabilization of p53 and transcriptional upregulation of p21, which binds and inhibits cyclin-CDK complexes
• faster: activates CHK2 and inactivates CDC25, thus inhibitory phosphates of E-CDK2 complex can no longer be removed

Question 16

Describe S phase checkpoint:

Answer 16

• DNA is surveillanced for damaged and breaks
• put on pause if any abnormalities are found
• example: BRCA1 repairs breaks in DNA

Question 17

If a normal, actively cycling cell receives damage to its DNA while it is in G1 phase, which of the following will function to arrest the cell cycle?

a) CDC25C phosphatase
b) cyclin D
c) CDK2
d) E2F
e) p21

Answer 17

p21

Question 18

If a normal, cycling cell is in S phase, which of the following proteins will be active?

a) BRCA1
b) CDK2
c) p21
d) p53
e) RB

Answer 18

CDK2

Question 19

Replication errors are deleted in a normal cell that has just completed S phase. The usual cellular response to this DNA damage will include:

a) binding of cyclin D to CDK2
b) halting the cell cycle at the restriction point
c) inactivation of CDC25C phosphatase
d) inhibition of purine nucleotide biosynthesis
e) RB binding to transcription factor E2F

Answer 19

inactivation of CDC25C phosphatase