Flashcards in EXAM2_L22_Regulation_of_Cell_Division Deck (14)
What required for activity?
cdk levels in the cell?
how many complexes active?
levels? when made? when degraded?
What is limitation of Cyclin-CDK?
-Phosphorylate Threonine/ Serine
-CDK levels remain constant/Cyclin levels vary
-one cdk-cyclin dominates at any given time
-synthesized only during phases when needed
-Determines which proteins phosphorylated by CDK
-cdk-c inhibited by CDKIs even if cyclin still bound to cdk
Cyclin-CDK limited to the phase where complex forms
What 3 checkpoints of focus?
What is each point dependent on?
1. Restriction point (g1)-- MITOGEN signals
2. g2-M Checkpoint--DNA proofreading
3. M-phase checkpoint (spindle assembly checkpoint)
-- Proper alignment of chromosomes in metaphase
How does cell cycle begin?
What signal? Where bind?
What activity activated? What does it make?
What TF activated?
What does it activate? What phase? why special?
MITOGEN (Growth factor- extracellular ligand binds)
-Ligand binds receptor tyrosine kinases
-phosphorylation cascade initiated (MAP kinase cascade)
-MAP kinase makes/activates transcription factor MYC
-MYC activates CYCLIN D (cyclin for g1 phase)
-Cyclin D-CDK4/6 is first active complex in cell cycle
G1 phase activation
mitogen>ras>map kinase cascade> MYC> CyclinD > CyclinD-CDK 4/6
When will the cell enter quiescent state G0?
How do cells re-enter the cycle?
Low Cyclin D
No CDK4/6 activity
Activate G0 to G1 cycle by:
--MITOGEN SIGNAL to make CYCLIN D
What 2 things required to pass g1 restriction point and proceed to S phase?
Why is this necessary?/what does it activate?
What does this activate? why important?
What is Rb? What named after? When will it present?
Both required to phosphorylate Rb
-Rb dissociates from E2F (TF) & E2F NOW ACTIVE
Rb- Tumor supressor protein
-named by "retinoblastoma"- cancer resulting from bad Rb gene
-Retinoblastoma AGE 0-4
Stepwise INACTIVATION of Rb:
1. Mitogens> Cyclin D > CyclinD-CDK4/6
2. CDK4/6 hypophosphorylates few THR/SER on Rb
3. gives low activity of E2F > Cyclin E> CyclinE-CDK2
4. CyclinE-CDK2 hyperphosphorylates Rb
5. E2F FREE to promote Transcription of S-phase
What regulates the completion of G1 and entry into S Phase?
phosphorylation state of Rb
cyclinD-CDK4/6 & cyclinE-CDK2 >phosphorylate Rb off of E2F (becomes active/uninhibited)
What regulates G2-M and M-phase checkpoints?
What required to pass G2-M checkpoint?
What required to pass M-phase checkpoint?
Passing G2->M checkpoint requires CyclinB-CDK1 ACTIVATION
Passing M-phase (spindle assembly) requires CyclinB-CDK1 DEACTIVATION
What is MPF? what is old name?
Maturation Promoting Factor (sometimes cdc2)
-Cyclin B-CDK1 Complex
Regulates G2-m and M checkpoints
Crossing G2-M checkpoint
What keeps CyclinBCDK1 inactivated during G2?
what activates it? How?
1. CyclinB-CDK1 (MPF) accumulated at end of G2
2. Phosphorylations of MPF keep it INACTIVE until ready
3. Dcd25 dephosphorylates MPF (now active)
4. M-phase Transition
Passing Spindle Assembly Checkpoint (M-phase)
APC= anaphase promoting complex
Why does CyclinB-CDK1 need to be DEACTIVATED?
## APC causes CyclinB and Cohesin DEGRADADATION
1. CyclinB degraded> MPF DEACTIVATED
2. APC Degrades Separase inhibitor> Separase Activated > Separase degrades Cohesin> chromatids separate
Mitosis requires CDK1 to be dephosphorylated ending mitosis. - possible by cyclinB degrading & phosphatases
7 CDKI's (Cyclin-Dependent Kinase Inhibitors)
2 Groups (what are they called?)
What are the 3 CDKI's?
What do each bind/inhibit?
What phase does each inhibit?
In environmental stress which is stimulated?
In DNA damage which is stimulated?
what promotes this CDKI?
What phase/point does this CDKI inhibit? How?
INK4 Group (inhibitors of CDK4/6)- G1 phase only
- p16 (environmental stress/sickness, starvation)
WAF1/CIP1 Group- (Stops Any phase)
-p21 (DNA damage)
-p51 promotes p21 mRNA>p21 protein>binds Cyclin & inhibits
- p21 inhibits cyclinE-CDK2 (stops Restriction point) by preventing Rb hyperphosphorylation