title: Conservation of a stress response: human heat shock transcription factors functionally substitute for yeast HSF.
abstract: Heat shock factors (HSF) are important eukaryotic stress responsive transcription factors which are highly structurally conserved from yeast to mammals. HSFs bind as homotrimers to conserved promoter DNA recognition sites called HSEs. The baker's yeast Saccharomyces cerevisiae possesses a single essential HSF gene, while distinct HSF isoforms have been identified in humans. To ascertain the degree of functional similarity between the yeast and human HSF proteins, human HSF1 and HSF2 were expressed in yeast cells lacking the endogenous HSF gene. We demonstrate that human HSF2, but not HSF1, homotrimerizes and functionally complements the viability defect associated with a deletion of the yeast HSF gene. However, derivatives of hHSF1 that give rise to a trimerized protein, through disruption of a carboxyl- or aminoterminal coiled-coil domain thought to engage in intramolecular interactions that maintain the protein in a monomeric state, functionally substitute for yeast HSF. Surprisingly, hHSF2 expressed in yeast activates target gene transcription in response to thermal stress. Moreover, hHSF1 and hHSF2 exhibit selectivity for transcriptional activation of two distinct yeast heat shock responsive genes, which correlate with previously established mammalian HSF DNA binding preferences in vitro. These results provide new insight into the function of human HSF isoforms, and demonstrate the remarkable functional conservation between yeast and human HSFs, critical transcription factors required for responses to physiological, pharmacological and environmental stresses.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606, USA.
authors.forename: X D
authors.initials: XD
authors.lastname: Liu
authors.forename: P C
authors.initials: PC
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Santoro
authors.forename: D J
authors.initials: DJ
authors.lastname: Thiele
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019143:Evolution, Molecular; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005816:Genetic Complementation Test; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D013045:Species Specificity; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C500769:CUP1-1 protein, S cerevisiae; D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C067168:HSF1 protein, S cerevisiae; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C007121:copper thionein; C070389:HSF2 protein, human; D008668:Metallothionein