Post-translational modifications of p53 tumor suppressor: determinants of its functional targets.

Tumor suppressor p53 functions as a "guardian of the genome" to prevent cells from transformation. p53 is constitutively ubiquitinated and degradated in unstressed conditions, thereby suppressing the expression. However, cellular stimuli enable p53 to escape from the negative regulation, and then stably expressed p53 transactivates its target genes to induce cell cycle arrest, DNA repair, or apoptosis. Promoter preference of target genes is determined by modification status of p53. Because p53 has two critical roles in the decision of cell fate, stopping cell cycle to repair damaged DNA or induction of apoptotic cell death in response to DNA damage, elucidation of switching mechanisms on p53 functions is of particular importance. Here we review recent evidence how several post-translational modifications of p53 including methylation, phosphorylation, acetylation, and ubiquitination, affect the functions of p53 in response to cellular stress.