Figure 2.

Regulation of wt and mutant p53 stability in response to stress. Wt and mutant p53 are maintained at basal levels by Mdm2-mediated degradation. Upon stress stimulus, events such as post-translational modifications (PTM) result in stabilization and accumulation of p53. During recovery from stress, wt p53 returns to basal levels as a result of negative feedback through Mdm2. However, mutant p53 accumulates due to its failure to transactivate Mdm2. Mutant p53 is also protected from Mdm2 and CHIP mediated ubiquitination by chaperone proteins. This can be overcome by treatment with Hsp90 inhibitors. Treatment of cells with As₂O₃ induces the E3 ligase Pirh2, which ubiquitinates mutant p53.