期刊
PLOS GENETICS
卷 13, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1007024
关键词
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资金
- Association Francaise contre las Myopathies, a European Union's Seventh Framework Programme/AIRC (Associazione Italiana per la Ricerca sul cancro) Reintegration
- Ligue Contre le Cancer (Comites de Savoie, Puy-de-Dome and Rhone)
- Foundation ARC
- European Research Council under the European Union's Seventh Framework Programme/ERC [616088]
- Israel Science Foundation [921/13]
- European Research Council (ERC) [616088] Funding Source: European Research Council (ERC)
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.
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