T1Q5: Cell Cycle Flashcards
Define the stages of the mammalian cell cycle and describe how protein kinases control the progression of the cell cycle. • Define the four major checkpoints and understand what event they monitor.
Mad2 1. checkpoint 2 action 3. regulation 4. significance
checkpoint: spindle (metaphase–>anaphase)
action: inactivate APC by binding to Cdc20 subunit
regulation: Bub1, Bub3, Mad1 phosphorylate (activate Mad2) if microtubules have not bound a kinetochore
sig: cells will not enter anaphase until all kinetochores are attached to the spindle
Cdc20
subunit of APC, binding of Mad2 renders the whole complex inactive
Bub1, Bub3, Mad1
kinases that activate Mad2 when microtubules bind to a kinetochore
they are inhibited when when microtubules bind to the kinetochore
p53
- checkpoint
- action
- regulation
checkpoint: DNA damage (G1&G2 phase)t
action: activates transcription of cyclin kinase inhibitor p21.
regulation:
no damage- Mdm2 poly-ubquinates p53 and leads to its destruction
damaged protein kinases (ATM/ATR and CHK1/2) phosphorylate it and spare it from destruction
p21
- checkpoint
- action
- regulation
checkpoint: DNA damage (G1&G2 phase)
action: Cdk inhibitor, blocks cyclin E/cdk which stops the cell from moving further
ATM/ATR + CHK1/2
func: activate during DNA damage to phosphorylate (activate) p53
checkpoint: DNA damage (G1&G2 phase)
Mad-2
checkpoint: Mitosis, Spindle (metaphase-anaphase)
cycles on and off the kinetochore
in it’s phosphorylated state is cock-blocks APC
Bub1, Bub3, and Mad1
checkpoint: Mitosis, Spindle (metaphase-anaphase)
phosphorylate mad2 when microtubules ARE NOT bound. Prevents anaphase before all chromosomes are lined up
Cdc20
checkpoint: Mitosis, Spindle (metaphase-anaphase)
the cyclin that pairs with APC
APC
1. checkpoint
checkpoint: Mitosis, Spindle (metaphase-anaphase)
a ubiquitin ligase that promotes anaphase by tagging cohesins and other proteins for destruction
MPF
1. checkpoint
2.
checkpoint: mitosis (G2-M)
CyclinB + cdk
mediates nuclear envelope break down, chromosome condensation and spindle assembly
APC
ubiquitin ligase that acts on mitotic scaffolds and cyclin B to end mitosis and promote G1
Rb
1. checkpoint
2 action
3. regulation/ significance
checkpoint: Start (G1-S)
binds to E2F and blocks its ability to promote the cell cycle
mutation causes RetinoBlastoma (Rb)
E2F
1. checkpoint
2 action
3. regulation/ significance
checkpoint: Start (G1-S)
transcription factor that activates START
inhibited by binding of unphosphorylated Rb
cdk4&cdk6
1. checkpoint
2 action
3. regulation/ significance
checkpoint: Start (G1-S)
Cyclin-D dependent enzymes that act on Rb to reduce its inhibition of E2F; initiate START
