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

Abstract

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.

An amphibian‐derived, cationic, α‐helical antimicrobial peptide kills yeast by caspase‐independent but AIF‐dependent programmed cell death

“…2B). Production of ROS was also much reduced in the deletion strains when exposed to 5 mM H2O2, particularly in stm1D, which is consistent with previous observations (Ligr et al, 2001).…”

“…The DsS3(1-16) affinity matrix also specifically purified Stm1p, a DNA-binding protein known to regulate PCD in yeast (Ligr et al, 2001), providing additional evidence that the inhibitory action of the peptide is due to the induction of PCD. Deletion of STM1 results in sensitivity to DNAdamaging agents but induces resistance to low concentrations of H 2O2.…”

“…Intriguingly, STM1, IZH2 and AIF1 have previously been implicated in the process of PCD/apopotosis in yeast; for example, Aif1p, or apoptosis-inducing factor, is a key regulator of cell death in mammalian cells and yeast ; Izh2p, a transmembrane, receptor-like protein that regulates lipid metabolism, controls apoptotic cell death induced by exposure to the plant defence peptide, osmotin (Narasimhan et al, 2005); and Stm1p, a DNA-binding protein that is involved in the control of apoptosis-like cell death in yeast (Ligr et al, 2001). Notably, none of these gene deletions displayed resistance to another unrelated a-helical, cationic peptide, magainin 2 from Xenopus laevis (Zasloff, 1987) (data not shown), indicating that the sensitivity to DsS3(1-16) conferred by these genes was not a general response to a-helical, cationic antimicrobial peptides.…”

Knockout of caspase-like gene, YCA1 , abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae

“…Results of recent investigations show that unicellular organisms also possess the ability to undergo programmed cell death (5-7). In particular, yeast Saccharomyces cerevisiae dies in an apoptoticlike manner in response to oxidative stress (8)(9)(10)(11). The budding yeast S. cerevisiae has emerged as a useful system for programmed cell death or apoptotic studies because it is readily amenable to genetic and molecular analysis (12).…”

Origin licensing and programmed cell death: a hypothesis

“…Whether programmed cell death occurs in yeast has been controversial, although accumulating evidence suggests this is the case. 27 In fact, recent studies suggest that apoptosis in budding yeast is regulated by the proteasome, 28 as well as by caspaserelated proteases. 29 Programmed cell death also occurs in prokaryotes, including Baccilus subtilis, where it plays an important role in sporulation.…”