p53-mediated apoptosis involves multiple mechanisms. A number of p53-regulated apoptosis-related genes have been identified. Some of these genes encode proteins that are important in controlling the integrity of mitochondria while the others code for membrane death receptors. p53 may also induce apoptosis by interfering with the growth factor-mediated survival signals. Although the transactivation-deficient p53 can induce apoptosis, evidence suggests that both the transcription-dependent and independent functions are needed for full apoptotic activity. p73 and p63 are two other members of the p53 family that show homology to p53 in their respective transactivation, DNA-binding and oligomerization domains. Both p73 and p63 transactivate p53-regulated promoters and induce apoptosis. Evidence suggests that both p73 and p63 may mediate apoptosis via some of the same mechanisms that are utilized by p53. However, both p73 and p63 exhibit features that are different from those of p53. Hence, both p73 and p63 are predicted to mediate apoptosis via mechanisms that are completely distinct from those engaged by p53. J. Cell. Physiol. 182:171-181, 2000. Published 2000 Wiley-Liss, Inc.