p53

Nicknamed the guardian of the genome, this tumor suppressor protein is a DNA binding protein that regulates transcription. Its domains are cell cycle regulation and DNA repair. Mutations of the p53 gene are found in 50% of all cancers. After DNA damage occurs, ATM (ataxia telangiectasia mutated) activates p53, which activates p21, GADD45, and, if necessary, BAX. P21 is a cyclin dependent kinase inhibitor, and it does G1 arrest, stopping the cell in G1 phase from proceeding to S phase. GADD45 repairs DNA damage. BAX signals apoptosis. MDM2, an ubiquitin ligase, stops p53 by ubiquinating it and so sending it to the proteasome. ARF/p14 inactivates MDM2. USP7, an ubiquitin specific protease, takes off the ubiquitin on p53. Radiation, a common treatment of cancer, won’t work on cancers including a mutation of p53. Epstein-Barr virus releases EBNA-1, which inactivates USP7. HPV uses E6 to ubiquinate p53 and E7 to take the place of E2F, which contain info for transcription enzymes, under the retinablastoma.