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 requir ed for growth in the presence of mutagens. Overexpression in cells with imp aired proteasomal degradation leads to cell death accompanied with cytologi cal markers of apoptosis: loss of plasma membrane asymmetry, chromatin cond ensation, and DNA cleavage. Cells lacking Stm display deficiency in the apo ptosis-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 mis sing from the cells or when inhibition of Stm1 synthesis permits proteasoma l degradation to decrease its amount in the cell. Conversely, Stm1 accumula tion induces cell death. In addition we identified five other genes whose o verexpression. in proteasomal mutants caused similar apoptotic phenotypes.