p53 Function

p53 Functions:

1) activation of DNA repair proteins

2) cell cycle control through cell arrest, cell senescence

3) apoptosis initiation (programmed cell death)

p53 Anti-Cancer Mechanisms

- p53 is normally bound to MDM2 (also known as HDM2)

- MDM2 is the negative regulator of p53

- MDM2 blocks p53 action and targets it for degradation through the common pathway, ubiquitination

- MDM2 targets p53 for destruction by marking it, through ligase activity

- DNA-damaging stimulate, such as UV radiation, activate DNA damage sensor proteins

- DNA damage sensor proteins include ATM, CHK1 and CHK2

- these proteins phosphorylate p53, preventing the binding of MDM2 to p53

- unbound p53 acts as a transcription activator

- transcription is activated for numerous genes, such as p21

- p21 acts on G1/S transition point complexes within the cell cycle, inhibiting there activity and halting cell growth and progression

- p21 binds to CDK (cell division stimulationg) protein complex

- p21 binding prevents a cell going onto the next stage of cell replication