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Role of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin.
Open accessAbstract
The role of HSP90 in stress tolerance was investigated in Saccharomyces cerevisiae. Cells showing 20-fold overexpression of Hsc82, an HSP90 homologue in yeast, were hypersensitive to high-NaCl or H-LiCl stresses. Hsc82-overexpressing cells appeared similar to calcineurin-defective cells in salt sensitivity and showed reduced levels of calcineurin-dependent gene expression. Co-overexpression of Cna2, the catalytic subunit of calcineurin, suppressed the hypersensitivity. Cna2 and Hsc82 coimmunoprecipitated from control cells grown under normal conditions but not from stressed cells. In contrast, coimmunoprecipitation was detected with Hsc82-overexpressing cells even after exposure to stresses. Cna2 immune complexes from stressed control cells showed a significant level of calcineurin activity, whereas those from stressed Hsc82-overexpressing cells did not. Treatment of extracts from Hsc82-overexpressing cells with Ca(2+)-calmodulin increased the calcineurin activity associated with Cna2 immune complexes. Geldanamycin, an inhibitor of HSP90 abolished the coimmunoprecipitation but did not activate calcineurin. When the expression level of Hsc82 decreased to below 30% of the normal level, cells also became hypersensitive to salt stress. In these cells, the amount of Cna2 was reduced, likely as a result of degradation. The present results showed that Hsc82 binds to and stabilizes Cna2 and that dissociation of Cna2 from Hsc82 is necessary for its activation.
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“Hsp90 stabilizes the catalytic subunit of calcineurin in both S. cerevisiae and C. albicans [41], [91], thereby enabling calcineurin-dependent responses to drug-induced cellular stress [3], [92].”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [91]
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“In S. cerevisiae, Hsp90 interacts physically with the catalytic subunit of calcineurin keeping it stable and poised for activation [23].”
From Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin (2009) · cites this paper as [23]
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“Consistent with previous findings [23], we confirmed that Hsp90 and calcineurin physically interact in S. cerevisiae (Figure 9A), as they do in C. albicans (Figure 4).”
From Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin (2009) · cites this paper as [23]
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Metadata
- Authors
- Imai, J., & Yahara, I.
- Affiliations
- Tokyo Metropolitan Institute of Medical Science (JP)
- Corresponding author
- Yahara, Ichiro
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-12-01
- Volume
- 20
- Issue
- 24
- Pages
- 9262-9270
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC102183
- OpenAlex
- W2138281171
- Cited by
- 123
- References
- 53
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 11 · 2013: 2 · 2012: 6
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Agricultural and Biological Sciences › Plant Science › Plant Stress Responses and Tolerance
- Keywords
- HSP90, calcineurin, salt tolerance, sodium chloride stress, protein stabilization, protein-protein interaction, geldanamycin, calcium/calmodulin, Saccharomyces cerevisiae
- MeSH terms
- Calcium-Binding Proteins, Canavanine, Cloning, Molecular, Culture Media, Heat-Shock Proteins, Phosphoprotein Phosphatases, Plasmids, Precipitin Tests, Saccharomyces cerevisiae, Salts, Temperature, Transformation, Genetic, Blotting, Western, HSP90 Heat-Shock Proteins, Calcineurin, Saccharomyces cerevisiae Proteins
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