Regulation of programmed cell death by the p53 pathway.

The p53 pathway is targeted for inactivation in most human cancers either directly or indirectly, highlighting its critical function as a tumor suppressor gene. p53 is normally activated by cellular stress and mediates a growth-suppressive response that involves cell cycle arrest and apoptosis. In the case of cell cycle arrest, p21 appears sufficient to block cell cycle progression out of G1 until repair has occurred or the cellular stress has been resolved. The p53-dependent apoptotic response is more complex and involves transcriptional activation of multiple proapoptotic target genes, tissue, and signal specificity, as well as additional events that are less well understood. In this chapter, we summarize the apoptosis pathway regulated by p53 and include some open questions in this field.