The proteasomal substrate Stm1 participates in apoptosis-like cell death in yeast.
We have identified the yeast gene STM1 in an overexpression screen for new proteasomal substrates. Stm1 is unstable in wild-type cells and stabilized in cells with defective proteasomal activity and thus a bona fide substrate of the proteasome. It is localized in the perinuclear region and is required for growth in the presence of mutagens. Overexpression in cells with impaired proteasomal degradation leads to cell death accompanied with cytological markers of apoptosis: loss of plasma membrane asymmetry, chromatin condensation, and DNA cleavage. Cells lacking Stm1 display deficiency in the apoptosis-like cell death process induced by treatment with low concentrations of H(2)O(2). We suggest that Stm1 is involved in the control of the apoptosis-like cell death in yeast. Survival is increased when Stm1 is completely missing from the cells or when inhibition of Stm1 synthesis permits proteasomal degradation to decrease its amount in the cell. Conversely, Stm1 accumulation induces cell death. In addition we identified five other genes whose overexpression in proteasomal mutants caused similar apoptotic phenotypes.
Ligr
M
M
Institut für Biochemie, Universität Stuttgart, 70569 Stuttgart, Germany.
Velten
I
I
Fröhlich
E
E
Madeo
F
F
Ledig
M
M
Fröhlich
K U
KU
Wolf
D H
DH
Hilt
W
W
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D016923:Cell Death; D002843:Chromatin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D039642:Eukaryotic Initiation Factors; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008856:Microscopy, Fluorescence; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010448:Peptide Initiation Factors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012316:RNA Nucleotidyltransferases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014466:Ultraviolet Rays
D000903:Antibiotics, Antineoplastic; D002843:Chromatin; D039642:Eukaryotic Initiation Factors; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D016877:Oxidants; D010448:Peptide Initiation Factors; D010726:Phosphodiesterase Inhibitors; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C083432:TIF3 protein, S cerevisiae; D001761:Bleomycin; D002110:Caffeine; D006861:Hydrogen Peroxide; D012316:RNA Nucleotidyltransferases; D003546:Cysteine Endopeptidases; C083706:PRE1 protein, S cerevisiae; D046988:Proteasome Endopeptidase Complex