Conservation of a stress response: human heat shock transcription factors functionally substitute for yeast HSF.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Liu, XD; Liu, PC; Santoro, N; Thiele, DJ

Published Date

  • November 1997

Published In

Volume / Issue

  • 16 / 21

Start / End Page

  • 6466 - 6477

PubMed ID

  • 9351828

Pubmed Central ID

  • 9351828

Electronic International Standard Serial Number (EISSN)

  • 1460-2075

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/16.21.6466

Language

  • eng