RRC ID 57334
著者 Robin M, Issa AR, Santos CC, Napoletano F, Petitgas C, Chatelain G, Ruby M, Walter L, Birman S, Domingos PM, Calvi BR, Mollereau B.
タイトル Drosophila p53 integrates the antagonism between autophagy and apoptosis in response to stress.
ジャーナル 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.
巻・号 15(5)
ページ 771-784
公開日 2019-5-1
DOI 10.1080/15548627.2018.1558001
PMID 30563404
PMC PMC6526837
MeSH 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*
IF 11.059
引用数 5
リソース情報
ショウジョウバエ