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Vol. 12, Issue 8, 2422-2432, August 2001
*Institut für Biochemie, Universität Stuttgart,
70569 Stuttgart, Germany; 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 H2O2. 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.
Anatomisches Institut,
Universität Tübingen, 72074 Tübingen, Germany; and
§Physiologisch-Chemisches Institut, Universität
Tübingen, 72076 Tübingen, Germany
These authors contributed equally to the study.
Corresponding author. E-mail address:
hilt{at}po.uni-stuttgart.de.
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