HIPK2-induced p53Ser46 phosphorylation activates the KILLER/DR5-mediated caspase-8 extrinsic apoptotic pathway.

The p53 oncosuppressor is the most common altered gene in human cancers and its regulation, in controlling cell cycle and apoptosis, is central in the problem of human tumorigenesis. In response to DNA damage p53 is activated mostly at the posttranslational level by complex series of modifications, including phosphorylation and acetylation, leading to control cell life and death. Apoptosis has recently been suggested to be a major contribution to p53-mediated suppression of tumor formation and resistance to apoptosis is one of the major hurdles in the treatment of cancer. The mechanisms by which p53 accomplishes its apoptotic function have been studied and involve activation of the mitochondrial pathway, the death receptor pathway, and cleavage of downstrean caspases. In this paper, we wanted to investigate whether HIPK2/p53 complex could induce the activation of extrinsic/death receptor pathway.