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

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

Autophagy (2018-12-20)
Marion Robin, Abdul Raouf Issa, Cristiana C Santos, Francesco Napoletano, Céline Petitgas, Gilles Chatelain, Mathilde Ruby, Ludivine Walter, Serge Birman, Pedro M Domingos, Brian R Calvi, Bertrand Mollereau
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.