p53 in cell cycle and apoptosis

The p53 tumor suppressor is the most commonly mutated gene In human cancer. The p53 protein is stabilized in response to different checkpoints activat ed by DNA damage, hypoxia, viral infection, or oncogene activation resultin g in diverse biological effects, such as cell cycle arrest, apoptosis, sene scence, differentiation and antiangiogenesis. The stable p53 protein is act ivated by phosphorylation, dephosphorylation and acetylation yielding a pot ent sequence-specific DNA-binding transcription factor. The wide range of p 53's biological effects can in part be explained by its activation of expre ssion of a number of target genes including p21 (WAF1), GADD45, 14-3-3 sigm a, bar, BTG2, PIG3, IGF-BP3 and others. p53 can induce or potentiate apopto sis through several mechanisms, both by regulating the expression of genes which can participate in the apoptotic response and through transcriptional ly independent means. There appears to be cell type variability in both the response to p53 expression and in the requirement for p53 transcriptional transactivation for the induction of apoptosis.