In the yeast heat shock response, Hsf1-directed induction of Hsp90 facilitates the activation of the Slt2 (Mpk1) mitogen-activated protein kinase required for cell integrity.
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Yeast is rendered temperature sensitive with loss of the C-terminal (CT) domain of heat shock transcription factor (Hsf1). This domain loss was found to abrogate heat stimulation of Slt2 (Mpk1), the mitogen-activated protein kinase that directs the reinforced cell integrity gene expression needed for high-temperature growth. In Hsf1 CT domain-deficient cells, Slt2 still undergoes Mkk1/2-directed dual-Thr/Tyr phosphorylation in response to the heat stimulation of cell integrity pathway signaling, but the low Hsp90 expression level suppresses any corresponding increase in Slt2 kinase activity due to Slt2 being a "client" of the Hsp90 chaperone. A non-Hsf1-directed Hsp90 overexpression restored the heat induction of Slt2 activity in these cells, as well as both Slt2-dependent (Rlm1, Swi4) and Slt2-independent (MBF) transcriptional activities. Their high-temperature growth was also rescued, not just by this Hsp90 overexpression but by osmotic stabilization, by the expression of a Slt2-independent form of the Rlm1 transcriptional regulator of cell integrity genes, and by a multicopy SLT2 gene vector. In providing the elevated Hsp90 needed for an efficient activation of Slt2, heat activation of Hsf1 indirectly facilitates (Slt2-directed) heat activation of yet another transcription factor (Rlm1). This provides an explanation as to why, in earlier transcript analysis compared to chromatin immunoprecipitation studies, many more genes of yeast displayed an Hsf1-dependent transcriptional activation by heat than bound Hsf1 directly. The levels of Hsp90 expression affecting transcription factor regulation by Hsp90 client protein kinases also provides a mechanistic model for how heat shock factor can influence the expression of several non-hsp genes in higher organisms.
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In S. cerevisiae, Hsp90 may interact with PKC signaling by chaperoning PKC and the MAPK Slt2.
“In S. cerevisiae, Hsp90 may also interact with PKC signaling by chaperoning PKC [48] and the MAPK Slt2 [49],[50].”
From Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin (2009) · cites this paper as [50]
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“cerevisiae, Hsp90 may also interact with PKC signaling by chaperoning PKC [48] and the MAPK Slt2 [49,50].”
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- Authors
- Truman, A. W., Millson, S. H., Nuttall, J. M., Mollapour, M., Prodromou, C., & Piper, P. W.
- Affiliations
- University of Sheffield (GB)
- Institute of Cancer Research (GB)
- Corresponding author
- Piper, Peter W.
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2007-04
- Volume
- 6
- Issue
- 4
- Pages
- 744-752
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC1865661
- OpenAlex
- W2154087334
- Cited by
- 59
- References
- 58
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 1 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 1 · 2014: 1 · 2012: 5
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Funders
- Wellcome Trust (074575)
- Biotechnology and Biological Sciences Research Council (C506721/1)
- 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 response, HSF1, HSP90, mitogen-activated protein kinase, cell integrity pathway, Hsp90 client proteins, Rlm1, Swi4, MBF, osmotic stabilization, temperature sensitivity, transcriptional activation, Saccharomyces cerevisiae
- MeSH terms
- DNA-Binding Proteins, Enzyme Activation, Heat-Shock Proteins, Phosphorylation, Saccharomyces cerevisiae, Temperature, Transcription Factors, Transcription, Genetic, Protein Structure, Tertiary, HSP90 Heat-Shock Proteins, Heat-Shock Response, Macrolides, Mitogen-Activated Protein Kinases, MADS Domain Proteins, Saccharomyces cerevisiae Proteins, MAP Kinase Kinase 1, Mutant Proteins
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