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 by DNA damage, hypoxia, viral infection, or oncogene activation resulting in diverse biological effects, such as cell cycle arrest, apoptosis, senescence, differentiation, and antiangiogenesis. The stable p53 protein is activated 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 expression of a number of target genes including p21WAF1, GADD45, 14-3-3Ï, bax, Fas/APO1, KILLER/ DR5, PIG3, Tsp1, IGF-BP3 and others. This review will focus on the transcriptiona l targets of p53, their regulation by p53, and their relative importance in carrying out the biological effects of p53.