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Drosophila p53 integrates the antagonism between autophagy and apoptosis in response to stress.

Research paper by Marion M Robin, Abdul Raouf AR Issa, Cristiana C CC Santos, Francesco F Napoletano, Céline C Petitgas, Gilles G Chatelain, Mathilde M Ruby, Ludivine L Walter, Serge S Birman, Pedro M PM Domingos, Brian R BR Calvi, Bertrand B Mollereau

Indexed on: 20 Dec '18Published on: 20 Dec '18Published in: Autophagy



Abstract

The tumor suppressor TP53/p53 is a known regulator of apoptosis and macroautophagy/autophagy. However, the molecular mechanism by which TP53 regulates 2 apparently incompatible processes remains unknown. We found that Drosophila lacking p53 displayed impaired autophagic flux, higher caspase activation and mortality in response to oxidative stress compared with wild-type flies. Moreover, autophagy and apoptosis were differentially regulated by the p53 (p53B) and ΔNp53 (p53A) isoforms: while the former induced autophagy in differentiated neurons, which protected against cell death, the latter inhibited autophagy by activating the caspases Dronc, Drice, and Dcp-1. Our results demonstrate that the differential use of p53 isoforms combined with the antagonism between apoptosis and autophagy ensures the generation of an appropriate p53 biological response to stress.