Hsf1 Activation Inhibits Rapamycin Resistance and TOR Signaling in Yeast Revealed by Combined Proteomic and Genetic Analysis

摘要: TOR kinases integrate environmental and nutritional signals to regulate cell growth in eukaryotic organisms. Here, we describe results from a study combining quantitative proteomics comparative expression analysis the budding yeast, S. cerevisiae, gain insights into function regulation. We profiled protein abundance changes under conditions of inhibition by rapamycin treatment, compared this data existing information for corresponding gene products measured variety yeast. Among proteins showing upon almost 90% them demonstrated homodirectional (i.e., similar direction) transcriptomic heat/oxidative stress. Because known downstream responses regulated Tor1/2 did not fully explain extent overlap between these two conditions, tested novel connections major regulators stress response pathway. Specifically, hypothesized that activation regulator(s) phenocopied sought identify putative inhibitor(s). tested, found cells (hsf1-R206S, F256S ssa1-3 ssa2-2) constitutively activated heat shock transcription factor 1, Hsf1, inhibited resistance. Further hsf1-R206S, allele revealed also displayed multiple phenotypes consistent with reduced signaling. Hsf1 targets elevated cells, deletion PIR3 YRO2 suppressed TOR-regulated phenotypes. In contrast our observations constitutive other responses, such as Msn2/4 Hyr1, inhibit Thus, propose inhibits resistance signaling via specific target genes cerevisiae. Additionally, highlight value analyses large-scale proteomic datasets reveal new regulatory connections.