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You are here: Home / Teams / Apoptosis and Neurogenetics - B. Mollereau / Publications / 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.

Marion Robin, Abdul R Issa, Cristiana C Santos, Francesco Napoletano, Celine Petitgas, Gilles Chatelain, Mathilde Ruby, Ludivine Walter, Serge Birman, Pedro M Domingos, Brian R Calvi, and Bertrand Mollereau (2018)

Autophagy.

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-typeflies. Moreover, autophagy and apoptosis were differentially regulated by the p53 (p53B) and DeltaNp53 (p53A) isoforms: while the former induced autophagy in differentiated neurons, which protected against cell death, the latter inhibitedautophagy 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.

 
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