Ste50 adaptor protein influences Ras/cAMP-driven stress-response and cell survival in Saccharomyces cerevisiae
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The Ste50 adaptor protein is involved in a variety of cellular pathways that yeast cells use to adapt rapidly to environmental changes. A highly activated Ras–cyclic AMP (cAMP) pathway by deletion of the high-affinity cAMP-dependent phosphodiesterase 2 (PDE2) leads to repression of a stress mediated response and cell survival. Here we show that inactivation of STE50 confers a synthetic genetic interaction with pde2Δ. A hyperosmotic stress growth defect of ste50Δ pde2Δ cells is exacerbated by extracellular cAMP or by galactose as the sole carbon source in the medium. The inactivation of the serine/threonine protein-kinase Akt homologue Sch9 increase stress resistance and extend chronological life span. By pde2Δ-dependent increase of the Ras–cAMP pathway activity, inactivation of STE50 results in an extreme shortening of life span and oxidative stress sensitivity of sch9Δ mutants. Furthermore, sch9Δ can promote transcription of the small heat shock protein HSP26 in a PDE2-dependent manner; however, sch9Δ can promote transcription of the mitochondrial superoxide dismutase SOD2 in a PDE2- and STE50-dependent manner. These data indicate that inactivation of STE50 influences stress tolerance in mutants of the Ras–cAMP pathway, which is a major determinant of intrinsic stress tolerance and cell survival of the Saccharomyces cerevisiae.
KeywordsSaccharomyces cerevisiae SCH9 PDE2 STE50 Life span
We would like to thank all members of our group for their helpful discussions. This work was partly supported by a grant from the Deutsche Forschungsgemeinschaft.
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