P53 has a direct pro-apoptotic action at the mitochondria

The basis for p53's striking apoptotic and tumor suppressive potency lies in its pleiotropism that includes transcription-dependent and -independent functions. p53 kills cells predominantly via the mitochondrial death pathway rather than the death receptor pathway (Schuler et al. 2001). p53 can mediate apoptosis by transcriptional activation of pro-apoptotic genes like the BH3- only proteins Noxa and Puma, Bax, p53 AIP1, Apaf-1, DRAL and PERP, and by transcriptional repression of Bcl2 and IAPs. For Noxa, Puma and PIDD, downregulation decreases - but does not abolish - the extent of death after stress. Of note, induction of these target gene products show variable kinetics, with some being delayed in their response (over 24 h), e.g. Bax and p53AIP1 (Attardi et al. 2000; Nakano et al. 2001). Analysis of p53-regulated global gene expression shows that the type, strength and kinetics of the target gene profiles depends on p53 levels, stress type and cell type (Zhao et al. 2000). This indicates that only individual genes will be chosen from the complex spectrum of potentially inducible genes to mediate a specific p53 response in a given physiological situation.