p53 Regulation

p53 Activation

- occurs mainly through DNA damage

- leads to N-terminal phosphorylation of p53 by protein kinases activated by cell stress

- once activated, p53 protein not targeted for degradation and accumulates in cell

- activated p53 changes conformationally, allowing it to bind DNA and activate transcription of genes

- MAPK family and ATR, Chk and CAK protein kinases activate p53

p53 Inactivation

- p53 is continously degradated

- basal level is to keep p53 low

- Mdm2 keeps p53 levels low by binding and localizing p53 to the cytosol for proteosome degradation

- deacetylase enzymes, Sirt1 and Sirt7 can deacetylate p53 in order to inhibit apoptosis