Cited by 61Heat shock proteins researchFungal and yeast genetics researchBacterial Genetics and Biotechnology

Mutated Yeast Heat Shock Transcription Factor Exhibits Elevated Basal Transcriptional Activation and Confers Metal Resistance

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Sewell, Andrew K., Yokoya, Fumihiko, Yu, Wei, Miyagawa, Terumi, Murayama, Tetsuo, Winge, Dennis R.·1995·Journal of Biological Chemistry

Abstract

Cadmium-resistant Saccharomyces cerevisiae strain 301N exhibits high basal as well as cadmium-induced expression of the CUP1 metallothionein gene. Since regulation of CUP1 is usually restricted to copper ions, our goal was to identify the factor responsible for the high metallothionein levels in strain 301N. The gene responsible for the observed phenotype is a spontaneously mutated heat shock transcription factor gene (HSF1). A double, semidominant HSF1 mutant with substitutions at codons 206 and 256 within the DNA-binding domain of the heat shock factor (HSF) confers two phenotypes. The first phenotype is elevated transcriptional activity of the HSF mutant (HSF301), which results in constitutive thermotolerance. A second HSF301 phenotype is enhanced binding affinity for the heat shock element (HSE) within the CUP1 5'-sequences, resulting in high basal transcription of metallothionein. The CUP1 HSE is a minimal heat shock element containing only two perfectly spaced inverted repeats of the basic nGAAn block. Cells containing HSF301 are resistant to cadmium salts. The single R206S mutation is responsible for the high affinity binding to the CUP1 HSE. In addition, the R206S HSF substitution exhibits constitutive transcriptional activation from a consensus HSE (HSE2). The F256Y substitution in HSF attenuates the effects of R206S on the consensus HSE2, but not on the CUP1 HSE.

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Crossref · 10.1074/jbc.270.42.25079

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  • Hsf1 is activated by hyperphosphorylation in response to specific environmental cues, which in some fungi include glucose starvation, superoxide, oxygen tension and changes in membrane lipid composition as well as heat shock.

    “Hsf1 is activated by hyperphosphorylation in response to specific environmental cues, which in some fungi include glucose starvation, superoxide, oxygen tension and changes in membrane lipid composition as well as heat shock10,39,45,46.”

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Authors
Sewell, A. K., Yokoya, F., Yu, W., Miyagawa, T., Murayama, T., & Winge, D. R.
Affiliations
  • University of Utah (US)
  • Ehime University (JP)
Corresponding author
Winge, Dennis R.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1995-10
Volume
270
Issue
42
Pages
25079-25086
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1991800467
Cited by
61
References
46
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2019: 1 · 2018: 2 · 2016: 1 · 2014: 2 · 2013: 2 · 2012: 4
FWCI
0.99
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA 61286, R01CA061286)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
heat shock transcription factor, HSF1, cadmium resistance, metallothionein, CUP1, heat shock element, DNA-binding domain, constitutive transcriptional activation, heat tolerance, Saccharomyces cerevisiae, metal resistance
MeSH terms
Base Sequence, Cadmium, Cloning, Molecular, DNA, DNA-Binding Proteins, Hot Temperature, Heat-Shock Proteins, Metallothionein, Molecular Sequence Data, Mutation, Saccharomyces cerevisiae, Transcription Factors, Transcriptional Activation, Saccharomyces cerevisiae Proteins

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