Robin, M., Issa, A.R., Santos, C.C., Napoletano, F., Petitgas, C., Chatelain, G., Ruby, M., Walter, L., Birman, S., Domingos, P.M., Calvi, B.R., Mollereau, B. (2019). Drosophila p53 integrates the antagonism between autophagy and apoptosis in response to stress.  Autophagy 15(5): 771--784.

FBrf0241963

Research paper

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.

PMC6526837 (PMC) (EuropePMC)