Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Carmona-Gutiérrez, D; Bauer, MA; Ring, J; Knauer, H; Eisenberg, T; Büttner, S; Ruckenstuhl, C; Reisenbichler, A; Magnes, C; Rechberger, GN; Birner-Gruenberger, R; Jungwirth, H; Fröhlich, KU; Sinner, F; Kroemer, G; Madeo, F.
The propeptide of yeast cathepsin D inhibits programmed necrosis.
Cell Death Dis. 2011; 2(16):e161-e161
Doi: 10.1038/cddis.2011.43
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- Co-authors Med Uni Graz
- Birner-Grünberger Ruth
- Ruckenstuhl Rudolf
- Sinner Frank Michael
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetylation -
- Apoptosis - genetics
- Aspartic Acid Endopeptidases - biosynthesis
- Aspartic Acid Endopeptidases - deficiency
- Aspartic Acid Endopeptidases - genetics
- Biogenic Polyamines - metabolism
- Cathepsin D - genetics
- Cathepsin D - metabolism
- Cell Survival -
- Cellular Senescence -
- Gene Deletion -
- Gene Expression -
- Histones - genetics
- Histones - metabolism
- Lysosomes - genetics
- Lysosomes - metabolism
- Necrosis - genetics
- Necrosis - metabolism
- Plasmids -
- Protein Engineering - methods
- Protein Precursors - genetics
- Protein Precursors - metabolism
- Protein Structure, Tertiary - genetics
- Saccharomyces cerevisiae - genetics
- Saccharomyces cerevisiae - metabolism
- Saccharomyces cerevisiae Proteins - biosynthesis
- Saccharomyces cerevisiae Proteins - genetics
- Sequence Homology, Amino Acid -
- Transfection -
- Find related publications in this database (Keywords)
- chronological aging
- yeast apoptosis
- yeast necrosis
- spermidine