Crosstalk between tumor suppressors p53 and PKCδ: Execution of the intrinsic apoptotic pathways

p53 and PKC delta are tumor suppressors that execute apoptotic mechanisms in response to various cellular stresses. p53 is a transcription factor that is frequently mutated in human cancers; it regulates apoptosis in transcription-dependent and-independent ways in response to genotoxic stresses. PKC delta is a serine/threonine protein kinase and mutated in human cancers. Available evidence shows that PKC delta activates p53 by direct and/or indirect mechanisms. Moreover, PKC delta is also implicated in the transcriptional regulation of p53 in response to DNA damage. Recent findings demonstrated that p53, in turn, binds onto the PKC delta promoter and induces its expression upon DNA damage to facilitate apoptosis. Both p53 and PKC delta are associated with the apoptotic mechanisms in the mitochondria by regulating Bcl-2 family proteins to provide mitochondrial outer membrane permeabilization. This review discusses the crosstalk between p53 and PKC delta in the context of apoptotic cell death and cancer therapy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.