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

Autophagy. 2019 May;15(5):771-784. doi: 10.1080/15548627.2018.1558001. Epub 2018 Dec 28.

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.

Keywords: Apoptosis; Parkinson disease; caspase; macroautophagy; neurodegenerative disease; oxidative stress; p53; photoreceptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis / genetics*
  • Autophagy / genetics*
  • Cells, Cultured
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology
  • Oxidative Stress / physiology*
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Protein Isoforms
  • Tumor Suppressor Protein p53