P53 in autophagy control

Abstract

p53 is a well known tumor suppressor recognized for its ability to cause cell senescence and apoptosis.1 The pro-senescence function of p53 is mainly mediated by its transcriptional activation of cell cycle inhibitors. The proapoptotic function of p53 is carried out at two levels: one is through the transcriptional activation of proapoptotic proteins such as Puma, Noxa and Bax, the other is independent of its nuclear function. It physically and functionally interacts with the multi-domain members of the Bcl-2 family of proteins at mitochondria to cause mitochondrial membrane permeabilization. Stimuli such as genotoxic, hypoxic, and oncogenic stress can cause transcriptional activation as well as cytosolic accumulation with mitochondrial localization of wild-type p53 that leads to rapid mitochondrial apoptosis. Both the cytostatic and cytocidal functions of p53 contribute to its tumor suppressor nature.Adding to its tumor suppressing activity, p53 has recently been found to also regulate autophagy.2,3 Auto...