The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Mutational Analysis of Hsp90 Function: Interactions with a Steroid Receptor and a Protein Kinase
Open accessAbstract
Hsp90 is a protein chaperone whose functions are focused on a specific set of target proteins. The nature of Hsp90's interactions with these proteins is poorly understood. To provide tools for examining these interactions, we have isolated eight broadly distributed temperature-sensitive (ts) point mutations in the Hsp90 gene (HSP82) of Saccharomyces cerevisiae. The mutants fall into two distinct classes. One has a classic ts phenotype, with nearly wild-type activity at 25 degrees C and a precipitous loss of function at 34 degrees C. The remaining seven mutants, in contrast, cause a general reduction in Hsp90 function and are ts because they do not provide the high level of function required for growth at high temperatures. The effects of these mutants on two target proteins, a transcription factor (glucocorticoid receptor) and a tyrosine kinase (pp60v-src), provided several insights on Hsp90 function. First, Hsp90 is not only required to help the glucocorticoid receptor achieve a hormone-activable state, it is continuously required to maintain that state. Second, Hsp90's function in the maturation of pp60v-src involves separable roles in protein accumulation and kinase activation. Thus, Hsp90 is an integral component of both the steroid receptor and kinase signaling pathways. Finally, all eight point mutants affect the activation of both the glucocorticoid receptor and pp60v-src, indicating that Hsp90 promotes the activity of these very different target proteins through common mechanisms.
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“This explains why mutations at interface I on either Hsp90 (G333, K414, K418, K419)21–23 or Hsp70 (R171, N174, D213)24 led to defective Hsp90-Hsp70 interaction, growth defects and impaired client maturation of GR, v-Src and luciferase (Fig. 1d, e, Extended Data Fig. 4c–h; see Supplementary Table 3 for equivalent yeast residue numbering).”
From Structure of Hsp90–Hsp70–Hop–GR reveals the Hsp90 client-loading mechanism (2022) · cites this paper as [21]
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“SHRs, including the glucocorticoid receptor (GR), are hormone-regulated transcription factors that depend on Hsp90 for function throughout their lifetimes5–10.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [9]
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“The glucocorticoid receptor (GR) is a model client that constantly depends on Hsp90 for activity4-9.”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [9]
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Cites
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Flagged first, then by citations
Research works printed but not linked: 3
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- 10.1128/mcb.13.9.5290-5300.1993 · DOI
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Items 401–422 of 422
Hsp90: Common Target for Diverse Antibiotics
Kalyanaraman, P. (2006) · SHAREOK (University of Oklahoma; Oklahoma State University; Central Oklahoma University)
Regulation of Fungal Drug Resistance and Morphogenesis by Lysine Deacetylases
Li, X. (2015) · TSpace (University of Toronto)
Using proteomics as a tool for the study of micronutrient metabolism
Wallace, E. R. (2004)
Psychosocial Stress and Addison's Disease
Wolf, J. M. (2006)
Targeting Hsp90 Function to Treat Cancer: Much More to Be Learned
Whitesell, L. J., & McLellan, C. A. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6401-2_13
“In these model organisms, impairment of chaperone function results in cell cycle arrest, dauer developmental arrest and male sterility respectively, in a manner that is dependent on the extent of Hsp90 compromise (Birnby et al., 2000; Nathan and Lindquist, 1995; Yue et al., 1999).”
BackgroundArmstrong, H. (2013) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3tc7r
Fowdar, K. (2017) · ResearchSpace (University of KwaZulu-Natal)
Regulation of alternative polyadenylation in Drosophila melanogaster
Oliveira, M. (2019) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/zrjc-r941
The adaptive potential of the middle domain of yeast Hsp90Preprint
Cote-Hammarlof, P. A., Fragata, I., Flynn, J. M., Mavor, D., Zeldovich, K. B., Bank, C., & Bolon, D. N. A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/832022
“Here we examine a 119 amino acid region (encompassing positions 291-409, Fig 1) of the yeast middle domain Hsp90, known to bind to many client proteins (Nathan and Lindquist 1995; Nathan et al. 1997; Meyer et al. 2003; Hawle et al. 2006; Hagn et al. 2011).”
BackgroundDifferentiation and gene regulation
(1996) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(96)80095-5
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Mollapour, M. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737482045.793572272
3.10 Chaperones and Protein Folding
Horwich, A. L., Büchner, J., Smock, R. G., Gierasch, L. M., & Saibil, H. R. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-374920-8.00313-1
Rios, E. I., & Johnson, J. L. (2026) · Cell Stress and Chaperones · doi:10.1016/j.cstres.2026.100164
Chaumonnot, K. (2020) · theses.fr (ABES) · doi:10.70675/af1ab439z66b0z4e99z854dz1e5d91f17f0a
Friend and foe?: metals as facilitators and disruptors of steroid nuclear receptor signaling
Siegel, K. R., & Kassotis, C. D. (2026) · Toxicological Sciences · doi:10.1093/toxsci/kfag106
Inhibition of Plasmodium DNA double strand repair by the combined action of 17-AAG and ML216
Tanishka, K., Tabassum, W., Rout, D. K., Mukherjee, M., & Bhattacharyya, M. K. (2026) · Frontiers in Parasitology · doi:10.3389/fpara.2026.1896831
“…yeast strains iG170Dhsp82 ( MATa can1 – 100 ade2 – 1 his3-11 , 15 leu2-3 , 112 trp1 – 1 ura3 – 1 hsp82 :: LEU2 hsc82 :: LEU2 HIS3 :: HSP82G170D ) (Nathan and Lindquist, 1995) and W303a ( MATa leu2-3 , 112 his3-11 , 15 ade2-1 , trp1 , ura3-1 ) (Williams et al., 2005) to generate the strains MMY1…”
Khamitkar, S. R., Bag, M., Kini, V. R., Singh, M., Sethi, B. K., & Bhattacharyya, S. (2026) · Frontiers in Parasitology · doi:10.3389/fpara.2026.1944050
COpy Number Variant quantifICation Tool v3.1
Shropshire, W. C., Lermi, N. O., Hanson, B., & Karras, G. I. (2024) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.10871209
Boucher, M.-J., Morisset, J., Vachon, P. H., Reed, J. C., Lain�, J., & Rivard, N. (2000) · Journal of Cellular Biochemistry · doi:10.1002/1097-4644(20001201)79:3
Metadata
- Authors
- Nathan, D. F., & Lindquist, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lindquist, Susan
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1995-07
- Volume
- 15
- Issue
- 7
- Pages
- 3917-3925
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC230631
- OpenAlex
- W2101287778
- Cited by
- 423
- References
- 56
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 12 · 2020: 14 · 2019: 14 · 2018: 9 · 2017: 8 · 2016: 11 · 2015: 5 · 2014: 14 · 2013: 11 · 2012: 15
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5f32gm014745-03)
- National Institute of General Medical Sciences (GM14745-02)
- 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 › Molecular Biology › Protein Structure and Dynamics
- Keywords
- HSP90, temperature-sensitive mutants, glucocorticoid receptor, pp60v-src, tyrosine kinase, steroid receptor signaling, kinase activation, Saccharomyces cerevisiae
- MeSH terms
- DNA Mutational Analysis, Hot Temperature, Heat-Shock Proteins, Phenotype, Protein Binding, Receptors, Glucocorticoid, Saccharomyces cerevisiae, Oncogene Protein pp60(v-src), Point Mutation, HSP90 Heat-Shock Proteins, Saccharomyces cerevisiae Proteins
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