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PLoS Genet. 2017 Sep 25;13(9):e1007024. doi: 10.1371/journal.pgen.1007024. eCollection 2017 Sep.

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

Author information

1
Laboratory of Biology and Modelling of the Cell, UMR5239 CNRS/Ecole Normale Supérieure de Lyon, INSERM U1210, UMS 3444 Biosciences Lyon Gerland, Université de Lyon, Lyon, France.
2
Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France.
3
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Abstract

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis.

PMID:
28945745
PMCID:
PMC5629030
DOI:
10.1371/journal.pgen.1007024
[Indexed for MEDLINE]
Free PMC Article

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