title: Kex1 protease is involved in yeast cell death induced by defective N-glycosylation, acetic acid, and chronological aging.
abstract: N-glycosylation in the endoplasmic reticulum is an essential protein modification and highly conserved in evolution from yeast to humans. The key step of this pathway is the transfer of the lipid-linked core oligosaccharide to the nascent polypeptide chain, catalyzed by the oligosaccharyltransferase complex. Temperature-sensitive oligosaccharyltransferase mutants of Saccharomyces cerevisiae at the restrictive temperature, such as wbp1-1, as well as wild-type cells in the presence of the N-glycosylation inhibitor tunicamycin display typical apoptotic phenotypes like nuclear condensation, DNA fragmentation, phosphatidylserine translocation, caspase-like activity, and reactive oxygen species accumulation. Since deletion of the yeast metacaspase YCA1 did not abrogate this death pathway, we postulated a different proteolytic process to be responsible. Here, we show that Kex1 protease is involved in the programmed cell death caused by defective N-glycosylation. Its disruption decreases caspase-like activity, production of reactive oxygen species, and fragmentation of mitochondria and, conversely, improves growth and survival of cells. Moreover, we demonstrate that Kex1 contributes also to the active cell death program induced by acetic acid stress or during chronological aging, suggesting that Kex1 plays a more general role in cellular suicide of yeast.
authors.affiliation: Lehrstuhl für Zellbiologie und Pflanzenphysiologie, Universität Regensburg, Universitätstrasse 31, 93053 Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hauptmann
authors.forename: Ludwig
authors.initials: L
authors.lastname: Lehle
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D005075:Biological Evolution; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D006031:Glycosylation / Q000187:drug effects; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D007202:Indicators and Reagents / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D046188:Protein Modification, Translational / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D007202:Indicators and Reagents; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D014415:Tunicamycin; D006602:Hexosyltransferases; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase; D002268:Carboxypeptidases; C078874:carboxypeptidase D; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; D019342:Acetic Acid