Diverse Cellular Functions of the Hsp90 Molecular Chaperone Uncovered Using Systems Approaches
Open accessAbstract
A comprehensive understanding of the cellular functions of the Hsp90 molecular chaperone has remained elusive. Although Hsp90 is essential, highly abundant under normal conditions, and further induced by environmental stress, only a limited number of Hsp90 "clients" have been identified. To define Hsp90 function, a panel of genome-wide chemical-genetic screens in Saccharomyces cerevisiae were combined with bioinformatic analyses. This approach identified several unanticipated functions of Hsp90 under normal conditions and in response to stress. Under normal growth conditions, Hsp90 plays a major role in various aspects of the secretory pathway and cellular transport; during environmental stress, Hsp90 is required for the cell cycle, meiosis, and cytokinesis. Importantly, biochemical and cell biological analyses validated several of these Hsp90-dependent functions, highlighting the potential of our integrated global approach to uncover chaperone functions in the cell.
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The fungal Hsp90 interactome displays a high degree of plasticity that depends on environmental conditions.
“The fungal Hsp90 interactome, which includes numerous client proteins such as receptors, protein kinases and transcription factors, displays a surprisingly high degree of plasticity that depends on environmental conditions.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [92]
The fungal Hsp90 interactome includes numerous client proteins such as receptors, protein kinases and transcription factors.
“The fungal Hsp90 interactome, which includes numerous client proteins such as receptors, protein kinases and transcription factors, displays a surprisingly high degree of plasticity that depends on environmental conditions.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [92]
Several key cell cycle regulators, including Swe1, Cdc28, Cdc50 and Cdc60, have been identified as Hsp90 interactors in S. cerevisiae.
“Several key cell cycle regulators have been identified as Hsp90 interactors in S. cerevisiae, including Swe1, Cdc28, Cdc50 and Cdc6061,92,123.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [92]
Hsp90 has evolutionarily conserved roles in cell cycle progression.
“Hsp90 also has evolutionarily conserved roles in cell cycle progression.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [92]
Many features of the Hsp90 interactome are highly conserved from yeast to humans despite substantial network rewiring over evolutionary time.
“Also, many features of the Hsp90 interactome are highly conserved from yeast to humans despite substantial network rewiring over evolutionary time.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [92]
Conserved features of the Hsp90 interactome include a preponderance of protein kinases and transcription factors as client proteins.
“These conserved features include a preponderance of protein kinases and transcription factors as client proteins67,78,91-93.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [92]
Hsp90's role in cell cycle progression appears to be conserved in the fungal kingdom.
“Hsp90's role in cell cycle progression appears to be conserved in the fungal kingdom. In the budding yeast Saccharomyces cerevisiae, Hsp90 is required for cell cycle progression during environmental stress, and in the fission yeast Schizosaccharomyces pombe Hsp90 interacts with cell cycle machinery (Aligue et al., 1994; Munoz and Jimenez, 1999; McClellan et al., 2007).”
From Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression in<i>Candida albicans</i> (2012) · cites this paper as McClellan et al., 2007
In S. cerevisiae, Cdc15 and Dbf2, two kinases in the MEN cascade, were identified in screens for Hsp90 interactors, and bub2 null mutants are hypersensitive to Hsp90 inhibitors, as are strains lacking the major MEN targets Sic1 and Cdh1.
“In S. cerevisiae, Cdc15 and Dbf2, two kinases in the MEN cascade, were identified in screens for Hsp90 interactors, and bub2 null mutants are hypersensitive to Hsp90 inhibitors, as are strains lacking the major MEN targets Sic1 and Cdh1 (Zhao et al., 2005; McClellan et al., 2007).”
From Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression in<i>Candida albicans</i> (2012) · cites this paper as McClellan et al., 2007
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- Authors
- McClellan, A. J., Xia, Y., Deutschbauer, A. M., Davis, R. W., Gerstein, M., & Frydman, J.
- Affiliations
- Stanford University (US)
- Yale University (US)
- Corresponding author
- Frydman, Judith
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 131
- Issue
- 1
- Pages
- 121-135
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2132919995
- Cited by
- 474
- References
- 56
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 21 · 2023: 9 · 2022: 20 · 2021: 26 · 2020: 32 · 2019: 33 · 2018: 27 · 2017: 33 · 2016: 23 · 2015: 29 · 2014: 32 · 2013: 31 · 2012: 41
- FWCI
- 9.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2116 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Jane Coffin Childs Memorial Fund for Medical Research
- National Institutes of Health
- National Institute of General Medical Sciences (GM 56433, F32GM064992, GM64992, P50GM062413)
- 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 › Ubiquitin and proteasome pathways
- Keywords
- HSP90, molecular chaperones, Saccharomyces cerevisiae, secretory pathway, cell transport, environmental stress response, cell cycle, meiosis, cytokinesis, chaperone activity
- MeSH terms
- Biological Transport, Cell Cycle, Saccharomyces cerevisiae, Reproducibility of Results, Genome, Fungal, Gene Deletion, HSP90 Heat-Shock Proteins, Computational Biology, Oligonucleotide Array Sequence Analysis, Secretory Vesicles, Saccharomyces cerevisiae Proteins, Gene Regulatory Networks
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