Fig. 3. Transcription-dependent and -independent mechanisms of p53-mediated apoptosis. In a cell-context-specific manner, p53 can activate the expression of pro-apoptotic genes and repress the transcription of pro-survival proteins (Ho and Benchimol, 2003). p53 can also translocate to the cytosol and associate with mitochondria. Direct effects of p53 on proteins of the Bcl-2 family have been proposed, as well as indirect effects through the upregulation of BH3-only proteins, p53AIP1 and ASC. In addition, p53 can promote the production of reactive oxygen species (ROS; Li et al., 1999) and activate caspases independently of mitochondria, perhaps through upregulation of PIDD (Lin et al., 2000), a protein involved in the activation of caspase-2 (Tinel and Tschopp, 2004).