Mutated Yeast Heat Shock Transcription Factor Exhibits Elevated Basal Transcriptional Activation and Confers Metal Resistance
Open accessAbstract
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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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.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [45]
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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
- hybrid
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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