Cell Cycle Flashcards
Entry to Cell Cycle
Mitogenic signals (eg. growth factors) releases CDK4/6 from inhibition by INK4 proteins (p15, p16)
G1 phase
CyclinD-CDK4/6 promote SEQUESTERS CyclinE-CDK2 inhibitors (CIP-KIP proteins (eg. p21 p27)
PHOSPHORYLATION of RB inactivates it - releases E2F TF, induces CycE-CDK2, hyperphosphorylates RB, positive feedback, drives G1-S transition
S phase
CyclinA-CDK2
G2 phase
CycA-CDK1
Mitosis
PLK activates phosphatase CDC25 which dephosphorylates and activates CycB-CDK1
PLK1 induces phosphorylation-dependent degradation of WEE1
CycB-CDK1 promotes CDC25 activity and WEE1 inhibition (positive feedback)
G1/S Checkpoint,
G2/M Checkpoint
ATR/ATM kinase phosphorylates and activates CHK1/2, phosphorylates and activates p53 which activate p21 (CIP-KIP), inhibiting CycE-CDK2
ATR/ATM kinase –> CHK1/CHK2 phosphorylation and activation
Phosphorylates and inactivates CDC25
Phosphorylates and activates p53 –> p21 –> Arrest