Cell Cycle, Cancer, and Cell Death Flashcards
What are stimuli that trigger active growth cycle or G0 stage? (5)
- growth factor receptors
- monitors of genome intergrity
- TGF-β receptors
- integrins
- monitors of cell metabolism
When will the amount of DNA in a cell be the least? the most?
- least: G1 phase
- most: after S phase, either G2 or M phases
What cyclins are a/w what cell cycle phases?
- G1: C, D1-3, E1-2, F, G
- S: A
- G2/M: B1-2
(cyclin H is constitutive)
What CDKs pair with what cyclins?
- CDK4/CDK6 = cyclin D
- CDK2 = cyclin E and A
- CDK1 = cyclin B
What protein is essential to CDK’s for cyclin bonding?
PSTAIRE α-helix
How is CDK activiated?
- cyclin-CDK complex
- CDK must be phosphorylated on one certain site, but desphosphorylated on other two sites
- protein phosphatase CDC25 dephosphorylates CDK’s
What are positive regulators of cell cycle? (4ish)
- CDK1
- CDK2
- CDK4/CDK6
- CDC25 A, B, and C phosphatases
How is the cell cycle negatively regulated?
- 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
What are negative regulators of cell cycle? (7 lol)
- p21 (CKI)
- p27 (CKI)
- p57 (CKI)
- p15 (INK4)
- p16 (INK4)
- p18 (INK4)
- p19 (INK4)
____ 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
Ras
What is the restriction point of cell cycle entry and progression?
cyclin D - CDK4/6 complex activating of cyclin E and binding of cyclin E to CDK2
Describe the G1/S transition:
- 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
Describe G2/M transition:
- 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
When do the 3 cell cycle checkpoints occur?
- G1 phase
- S phase
- G2 phase
Describe G1 checkpoint in terms of DNA damage and its 2 pathways:
- 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
Describe S phase checkpoint:
- DNA is surveillanced for damaged and breaks
- put on pause if any abnormalities are found
- example: BRCA1 repairs breaks in DNA
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
p21
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
CDK2
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
inactivation of CDC25C phosphatase
