A large number of p53-transcribed proteins have been shown to mediate growth arrest and/or apoptosis in vitro, whereas their in vivo roles remain largely unclear. p53 is capable of initiating apoptosis without transcription of apoptosis inducer genes, although the underlying mechanism is unknown. p53 is present in the mitochondria and appears to contribute to the biogenesis, function and apoptosis of this organelle. We have recently cloned a p53-binding mitochondrial WW domain-containing oxidoreductase (WOX1). Suppression of WOX1 expression abolishes p53 apoptotic function, indicating that WOX1 is a likely partner of p53 in cell death. In this review article, the potential role of WOX1/p53 as a signaling complex in the mitochondrial apoptosis is discussed.

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