HSP90: The Rosetta stone for cellular protein dynamics?
Open accessAbstract
The Hsp90 proteomic network is expansive and includes a variety of cell processes operating within the cytoplasm and nucleoplasm. Though the functional significance of the extensive interactions has not been defined, we suggest that the Hsp90 molecular chaperone machinery promotes dynamic behaviors for client proteins that is critical to achieve homeostasis. A general rapid action by cell factors would permit both proper assembly of biological complexes and efficient transitions between distinct structures. Here, we describe why the properties that are inherent to molecular chaperones place these proteins in a unique position to drive the dynamic cellular environment.
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Reshaping of dynamic client interactions upon Hsp90 conformational changes is critical for promoting structural transitions of the bound clients.
“Reshaping of dynamic client interactions upon Hsp90 conformational changes is critical for promoting structural transitions of the bound clients (71, 72).”
From Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network (2021) · cites this paper as [71]
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“Hsp90 chaperones hundreds of intracellular proteins [40–42] (http://www.”
TORC 1‐mediated sensing of chaperone activity alters glucose metabolism and extends lifespan
Perić, M., Lovrić, A., Šarić, A., Musa, M., Dib, P. B., Rudan, M., Nikolić, A., Sobočanec, S., Mikecin, A., Dennerlein, S., et al. (2017) · Aging Cell · doi:10.1111/acel.12623 · Cited by 24 · see citing works
Antibodies to Heat Shock Proteins 90α and 90β in Psoriasis
Damasiewicz-Bodzek, A., Szumska, M., & Tyrpień-Golder, K. (2020) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-020-00573-7 · Cited by 24 · see citing works
“2004), takes part in processes of DNA and RNA metabolism (Dezwaan and Freeman 2008; Powers and Workman 2007) and is also engaged in oncogenesis (in facilitating malignant transformation and maintaining malignant phenotype) (Bagatell and Whitesell 2004; Staufer and Stoeltying 2010).”
BackgroundNarayan, V., Eckert, M. J., Żylicz, M., Żylicz, M., & Ball, K. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.019505 · Cited by 23 · see citing works
Low dose Hsp90 inhibitor 17AAG protects neural progenitor cells from ischemia induced death
Bradley, E., Zhao, X., Wang, R., Brann, D. W., Bieberich, E., & Wang, G. (2014) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-014-0247-5 · Cited by 21 · see citing works
Unique proline-rich domain regulates the chaperone function of AIPL1.
Li, J., Žoldák, G., Kriehuber, T., Soroka, J., Schmid, F., Richter, K., & Buchner, J. (2013) · Biochemistry · doi:10.1021/bi301648q · Cited by 20 · see citing works
The Nuclear and DNA-Associated Molecular Chaperone NetworkPreprint
Gvozdenov, Z., Kolhe, J. A., & Freeman, B. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034009 · Cited by 19 · see citing works
Self-citationWang, C., Li, H.-F., Wang, X., Li, W.-G., Su, Q., Xiao, X., Hao, T., Chen, W., Zhang, Y., Zhang, H.-Y., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.60674 · Cited by 20 · see citing works
Regulation of PIDD auto-proteolysis and activity by the molecular chaperone Hsp90
Tinel, A., Eckert, M., Logette, E., et al. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.124 · Cited by 17 · see citing works
Geldanamycin-Induced PCNA Degradation in Isolated Hsp90 Complex from Cancer Cells
Wang, X., Heuvelman, D. M., Carroll, J. A., Dufield, D. R., & Masferrer, J. L. (2010) · Cancer Investigation · doi:10.3109/07357901003630983 · Cited by 16 · see citing works
Hsp90 Directly Modulates the Spatial Distribution of AF9/MLLT3 and Affects Target Gene Expression*
Lin, J. J., & Hemenway, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.101642 · Cited by 20 · see citing works
Hsp70/Hsp90 Organising Protein (Hop): Coordinating Much More than Chaperones
Schwarz, K., Baindur‐Hudson, S., Blatch, G. L., & Edkins, A. L. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-14740-1_3 · Cited by 13 · see citing works
Giannoulis, A., Feintuch, A., Unger, T., Amir, S., & Goldfarb, D. (2021) · Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.1c03641 · Cited by 8 · see citing works
Lu, X., Wang, L., & Ruden, D. M. (2012) · Pharmaceuticals · doi:10.3390/ph5090890 · Cited by 11 · see citing works
Molecular Chaperone-Mediated Nuclear Protein Dynamics
Echtenkamp, F., & Freeman, B. (2014) · Current Protein and Peptide Science · doi:10.2174/1389203715666140331112230 · Cited by 8 · see citing works
Self-citationGbHSP90 act as a dual functional role regulated in telomere stability in Ginkgo biloba
Feng, Y., Guo, X., Luo, M., Sun, Y., Sun, L., Zhang, H., Zou, Y., Liu, D., & Lu, H. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.135240 · Cited by 5 · see citing works
TRiC/CCT chaperonin governs RNA polymerase II activity in the nucleus to support RNA homeostasis
Gvozdenov, Z., Biswas, A., Peng, A. Y. T., Barcutean, Z., Gestaut, D. R., Frydman, J., Struhl, K., & Freeman, B. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.08.015 · Cited by 3 · see citing works
Self-citationClaassen, I., Adrita, N., Chandler, K. B., Black, S. M., Roberts, B. R., Estévez, Á. G., Beckman, J. S., & Franco, M. C. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104223 · Cited by 4 · see citing works
The disruption of proteostasis in neurodegenerative disorders
Jalles, A., & Maciel, P. (2015) · AIMS molecular science · doi:10.3934/molsci.2015.3.259 · Cited by 3 · see citing works
“Many of them (HSP70, HOP, etc) contain nuclear localization signals and can be imported into the nucleus by RanGTP-mediated mechanism in ambient growth conditions such as cell cycle and import of nuclear proteins [147,148,149].”
Combined Effects of Ambient PM2.5 and Cold Exposure on the Development of Metabolic Disorder
Liu, Z., Zhang, J., Fan, D., Wang, G., Wu, B., Lei, L., Wang, L., Zhao, J., & Chen, J. (2023) · Atmosphere · doi:10.3390/atmos14071157 · Cited by 2 · see citing works
Emergence and Characterization of the p23 Molecular Chaperone
Echtenkamp, F., & Freeman, B. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1130-1_9 · Cited by 1 · see citing works
Self-citationModulation of Amyloid Propagation in Yeast by Hsp70 and its Regulators and Chaperone Partners
Masison, D. C. (2011) · doi:10.1002/9781118063903.ch9 · Cited by 1 · see citing works
Biochemical analysis of proteins in the telomere maintenance pathway
DeZwaan, D. C. (2011) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Self-citationIDENTIFICATION OF NOVEL HEAT SHOCK RESPONSE MODULATORS FOR EXPERIMENTAL ANTI-MELANOMA INTERVENTION
Davis, A. L. (2015) · UA Campus Repository (The University of Arizona)
Structural Basis for Ternary Complex Formation Between tau, Hsp90, and FKBP51
Barrett, A. S., Wu, H.-W., Kashtanov, S., & Daughdrill, G. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2012.11.2162
“Typically, co-chaperone complexes containing Hsp90 can bind a variety of clients with different functions [20,54,55].”
BackgroundLu, X., Wang, L., Sollars, V. E., Garfinkel, M. D., & Ruden, D. M. (2013) · Springer eBooks · doi:10.1007/978-1-4614-6280-4_5
Chemical and Pharmacological Modulation of Telomerase
Soares, J. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/fgzz-7e09
Hsp90: A Target for Susceptibilities and Substitutions in Biotechnological and Medicinal Application
Warnecke, A., Kirschning, A., Landsberg, D., & Zeilinger, C. (2019) · Heat shock proteins · doi:10.1007/978-3-030-23158-3_18
Complex structure of human Hsp90N and a novel small inhibitor FS5
Liu, R., Lu, X.-L., Huang, X., He, W., Duan, J., Zhang, J., & Li, J. (2020) · Nuclear Science and Techniques · doi:10.1007/s41365-020-0739-3
Huo, M., Zhang, C., Wang, C., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-130892/v1
“HSP90 and its associated co-chaperones play key nucleic functions including chromatin remodeling, DNA transcription, RNA processing, DNA replication, telomere maintenance, and DNA repair[17, 18].”
BackgroundNew therapeutic targets in human acute myeloid leukemia
Reikvam, H. (2012) · NORA - Norwegian Open Research Archives
- Authors
- DeZwaan, D. C., & Freeman, B. C.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- ORCID
- Freeman, Brian C.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2008-04-15
- Volume
- 7
- Issue
- 8
- Pages
- 1006-1012
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W1989391398
- Cited by
- 73
- References
- 0
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 6 · 2012: 8
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of Illinois at Urbana-Champaign
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074270, DK074270)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- HSP90, molecular chaperones, client proteins, protein dynamics, chaperone-client interactions, proteostasis, protein complex formation, proteomic networks
- MeSH terms
- Homeostasis, Models, Biological, Telomere, Molecular Chaperones, HSP90 Heat-Shock Proteins, Multiprotein Complexes, Metabolic Networks and Pathways
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