title: Sir2 links the unfolded protein response and the heat shock response in a stress response network.
abstract: The Heat Shock Response (HSR) in the cytosol and the Unfolded Protein Response (UPR) in the endoplasmic reticulum are major pathways of the cellular proteostasis network. In Saccharomyces cerevisiae, HSR is regulated by transcription factor Hsf1, and UPR Ire1 branch activates transcription factor Hac1. Here we demonstrate systemic regulation of proteostasis through a direct link between UPR and HSR. Hsf1 is activated by UPR and its HSR depends on intact UPR. This link is mediated by Sir2, which is not only essential for Hsf1 HSR but also required for Hsf1 activation by UPR. Excess Sir2 augments Hsf1 activation by UPR and can compensate for its impairment in UPR-defective strains. Sir2 is upregulated by UPR but, in turn, it also attenuates this pathway, ensuring that UPR functions only transiently.
authors.affiliation: Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Weindling
authors.affiliation: Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel. Electronic address: shoshbn@tauex.tau.ac.il.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Bar-Nun
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C091341:HAC1 protein, S cerevisiae; C067168:HSF1 protein, S cerevisiae; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D014157:Transcription Factors; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2
keywords: HSR; Hsf1; Sir2; UPR