Post-translational Modifications of the p53 Transcription Factor

The p53 tumor suppressor acts as a potent transcription factor in response to bombardment by a variety of cellular stresses. Its importance in maintaining genomic stability and exerting anit-proliferative effects is underscored by the fact that it is found mutated in approximately 50% of all human tumors. p53 is tightly regulated at the post-translational level though multiple modifications including ubiquitination, phosphorylation, acetylation, and neddylation. Mdm2 is a key regulator of p53 by acting as a specific E3 ligase on the protein and targeting it to the ubiquitin-proteasome pathway. Together, these two proteins provide a critical node in the cellular circuitry for countless signaling pathways to converge.