Regulation of p53 downstream genes

The p53 tumor suppressor is the most commonly mutated gene in human cancer, p53 protein is stabilized in response to different checkpoints activated b y DNA damage, hypoxia, viral infection, or oncogene activation resulting in diverse biological effects, such as cell cycle arrest, apoptosis, senescen ce, differentiation and antiangiogenesis. The stable p53 protein is activat ed by phosphorylation, dephosphorylation and acetylation yielding a potent sequence-specific DNA-binding transcription factor. The wide range of p53's biological effects can in part be explained by its activation of expressio n of a number of target genes including p21(WAFI), GADD45, 14-3-3 sigma, ba r, Fas/APO1, KILLER/DR5, PIG3, Tsp1, IGF-BP3 and others. This review will f ocus on the transcriptional targets of p53, their regulation: by p53, and t heir relative importance in carrying out the biological effects of p53.