Journal
CELL DEATH & DISEASE
Volume 2, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2011.43
Keywords
chronological aging; yeast apoptosis; yeast necrosis; spermidine
Categories
Funding
- Austrian Science Fund FWF (Austria) [S-9304-B05, T414-B09]
- European Commission
- Ligue Nationale contre le Cancer (Equipe labellisee)
- Agence Nationale pour la Recherche (ANR)
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer (INCa)
- Canceropole Ile-de-France
- Austrian Science Fund (FWF) [W 901] Funding Source: researchfish
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The lysosomal endoprotease cathepsin D (CatD) is an essential player in general protein turnover and specific peptide processing. CatD-deficiency is associated with neurodegenerative diseases, whereas elevated CatD levels correlate with tumor malignancy and cancer cell survival. Here, we show that the CatD ortholog of the budding yeast Saccharomyces cerevisiae (Pep4p) harbors a dual cytoprotective function, composed of an anti-apoptotic part, conferred by its proteolytic capacity, and an anti-necrotic part, which resides in the protein's proteolytically inactive propeptide. Thus, deletion of PEP4 resulted in both apoptotic and necrotic cell death during chronological aging. Conversely, prolonged overexpression of Pep4p extended chronological lifespan specifically through the protein's anti-necrotic function. This function, which triggered histone hypoacetylation, was dependent on polyamine biosynthesis and was exerted via enhanced intracellular levels of putrescine, spermidine and its precursor S-adenosyl-methionine. Altogether, these data discriminate two pro-survival functions of yeast CatD and provide first insight into the physiological regulation of programmed necrosis in yeast. Cell Death and Disease (2011) 2, e161; doi:10.1038/cddis.2011.43; published online 19 May 2011
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