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Vol. 12, Issue 8, 2422-2432, August 2001

The Proteasomal Substrate Stm1 Participates in Apoptosis-like Cell Death in Yeast

Martin Ligr,^* Iris Velten,^* Eleonore Fröhlich, Frank Madeo,^§ Matthias Ledig,^* Kai-Uwe Fröhlich,^§ Dieter H. Wolf,^* and Wolfgang Hilt^*

 ^*Institut für Biochemie, Universität Stuttgart, 70569 Stuttgart, Germany;  Anatomisches Institut, Universität Tübingen, 72074 Tübingen, Germany; and  ^§Physiologisch-Chemisches Institut, Universität Tübingen, 72076 Tübingen, 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.

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These authors contributed equally to the study.

Corresponding author. E-mail address: hilt{at}po.uni-stuttgart.de.

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Molecular Biology of the Cell
Vol. 12, 2422-2432, August 2001
Copyright © 2001 by The American Society for Cell Biology

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