Quantitative Analysis of Hsp90-Client Interactions Reveals Principles of Substrate Recognition
Open accessAbstract
HSP90 is a molecular chaperone that associates with numerous substrate proteins called clients. It plays many important roles in human biology and medicine, but determinants of client recognition by HSP90 have remained frustratingly elusive. We systematically and quantitatively surveyed most human kinases, transcription factors, and E3 ligases for interaction with HSP90 and its cochaperone CDC37. Unexpectedly, many more kinases than transcription factors bound HSP90. CDC37 interacted with kinases, but not with transcription factors or E3 ligases. HSP90::kinase interactions varied continuously over a 100-fold range and provided a platform to study client protein recognition. In wild-type clients, HSP90 did not bind particular sequence motifs, but rather associated with intrinsically unstable kinases. Stabilization of the kinase in either its active or inactive conformation with diverse small molecules decreased HSP90 association. Our results establish HSP90 client recognition as a combinatorial process: CDC37 provides recognition of the kinase family, whereas thermodynamic parameters determine client binding within the family.
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Hsp90 is required for functional maturation of about 10% of the eukaryotic proteome, including signaling proteins such as GR.
“Hsp90 is required for the functional maturation of ~10% of the eukaryotic proteome, including signaling proteins such as GR, a steroid hormone receptor (SHR)1,3,13.”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [3]
The Introduction (p. 2) says HSP90 promotes the folding and function of diverse client proteins, including steroid hormone receptors. The discussion of steroid hormone chaperoning (p. 13) describes how HSP90 helps a receptor maintain a ligand-binding conformation. Our copy does not establish that HSP90 is required for functional maturation of approximately 10% of the eukaryotic proteome, or specifically identify GR as an example in that account. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHsp90 is an essential conserved chaperone that folds and activates many client proteins.
“Hsp90 is a conserved and essential molecular chaperone responsible for the folding and activation of hundreds of ‘client’ proteins1-3.”
From Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism (2022) · cites this paper as [3]
Hsp90 clients are enriched in signaling proteins such as steroid hormone receptors, making Hsp90 an important clinical target.
“Hsp90 ‘clients’ are enriched in signaling proteins, such as steroid hormone receptors (SHRs), making Hsp90 an important clinical target2–4.”
From Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor (2023) · cites this paper as [3]
Hsp90 plays a crucial role in protein homeostasis by regulating the folding and activity of a set of proteins known as clients.
“The molecular chaperone Hsp90 plays a crucial role in protein homeostasis by regulating the folding and activity of a set of proteins known as clients (1–3).”
From Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network (2021) · cites this paper as [3]
Hsp90 promotes the maturation of diverse metastable signal transduction proteins, including kinases, phosphatases, and ubiquitin ligases (Hsp90 clients), which function in many stress response pathways.
“Hsp90 promotes the maturation of a diverse array of metastable signal transduction proteins, including kinases, phosphatases, and ubiquitin ligases (known as Hsp90 clients) [32]. These function in many stress response pathways.”
From Fitness Trade-offs Restrict the Evolution of Resistance to Amphotericin B (2013) · cites this paper as [32]
Hsp90 associates with more than one-half of the human kinome.
“estimates suggesting that Hsp90 associates with more than one-half of the human kinome (Taipale et al., 2012”
From Functional Genomic Screening Reveals Core Modulators of Echinocandin Stress Responses in Candida albicans (2018) · cites this paper as Taipale et al., 2012
Other studies identify only select kinases within a signaling cascade as Hsp90 clients.
“This is in contrast to other studies that identify only select kinases within a signaling cascade as Hsp90 clients (Taipale et al., 2012”
From Functional Genomic Screening Reveals Core Modulators of Echinocandin Stress Responses in Candida albicans (2018) · cites this paper as Taipale et al., 2012
Protein kinases are core transducers of cellular stress and a major class of Hsp90 client proteins.
“Protein kinases are core transducers of cellular stress and a major class of Hsp90 client proteins”
From Functional Genomic Screening Reveals Core Modulators of Echinocandin Stress Responses in Candida albicans (2018) · cites this paper as Taipale et al., 2012
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Cites
The protein kinase complement of the human genome
Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145 · see citing works
Hsp90 as a capacitor for morphological evolution
Rutherford, S. L., & Lindquist, S. (1998) · Nature · doi:10.1038/24550 · Cited by 2,270 · see citing works
Self-citationThe Genetic Landscape of a Cell
Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E. D., Sevier, C. S., Ding, H., Koh, J. L. Y., Toufighi, K., Mostafavi, S., et al. (2010) · Science · doi:10.1126/science.1180823 · Cited by 2,162 · see citing works
HSP90 at the hub of protein homeostasis: emerging mechanistic insights
Taipale, M., Jarosz, D. F., & Lindquist, S. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2918 · Cited by 1,818 · see citing works
Self-citationA census of human transcription factors: function, expression and evolution
Vaquerizas, J. M., Kummerfeld, S. K., Teichmann, S. A., & Luscombe, N. M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2538 · Cited by 1,573 · see citing works
COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460 · see citing works
Hsp90 as a capacitor of phenotypic variation
Queitsch, C., Sangster, T. A., & Lindquist, S. (2002) · Nature · doi:10.1038/nature749 · Cited by 1,372 · see citing works
Self-citationA Helix Propensity Scale Based on Experimental Studies of Peptides and Proteins
Pace, C. N., & Scholtz, J. M. (1998) · Biophysical Journal · doi:10.1016/s0006-3495(98)77529-0 · Cited by 1,074 · see citing works
Protein kinases: evolution of dynamic regulatory proteins
Taylor, S. S., & Kornev, A. P. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.09.006 · Cited by 940 · see citing works
Li, W., Bengtson, M. H., Ulbrich, A., Matsuda, A., Reddy, V. A., Orth, A. P., Chanda, S. K., Batalov, S., & Joazeiro, C. A. P. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001487 · Cited by 839 · see citing works
High-Throughput Mapping of a Dynamic Signaling Network in Mammalian Cells
Barrios‐Rodiles, M., Brown, K. R., Ozdamar, B., Bose, R., Liu, Z., Donovan, R. S., Shinjo, F., Liu, Y., Dembowy, J., Taylor, I. W., et al. (2005) · Science · doi:10.1126/science.1105776 · Cited by 726 · see citing works
Hsc70/Hsp90 Chaperone Machinery Mediates ATP-Dependent RISC Loading of Small RNA Duplexes
Iwasaki, S., Kobayashi, M., Yoda, M., Sakaguchi, Y., Katsuma, S., Suzuki, T., & Tomari, Y. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.015 · Cited by 507 · see citing works
Allosteric inhibitors of Bcr-abl–dependent cell proliferation
Adrián, F., Ding, Q., Sim, T., Velentza, A. V., Sloan, C., Liu, Y., Zhang, G., Hur, W., Ding, S., Manley, P. W., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio760 · Cited by 381 · see citing works
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases
Fedorov, O., Marsden, B. D., Pogačić, V., Rellos, P., Müller, S., Bullock, A. N., Schwaller, J., Sundström, M., & Knapp, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708800104 · Cited by 361 · see citing works
Hsp90 and Environmental Stress Transform the Adaptive Value of Natural Genetic Variation
Jarosz, D. F., & Lindquist, S. (2010) · Science · doi:10.1126/science.1195487 · Cited by 346 · see citing works
Self-citationConformational dynamics of the molecular chaperone Hsp90
Krukenberg, K. A., Street, T. O., Lavery, L. A., & Agard, D. A. (2011) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583510000314 · Cited by 308 · see citing works
Structure of an Hsp90-Cdc37-Cdk4 Complex
Vaughan, C. K., Gohlke, U., Sobott, F., Good, V. M., Ali, M. M. U., Prodromou, C., Robinson, C. V., Saibil, H. R., & Pearl, L. H. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.07.016 · Cited by 293 · see citing works
A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases.
Chen, H.-B., Ma, J.-H., Li, W., Eliseenkova, A. V., Xu, C.-F., Neubert, T., Miller, W., & Mohammadi, M. (2007) · Molecules and Cells · doi:10.1016/j.molcel.2007.06.028 · Cited by 290 · see citing works
Boulon, S., Pradet‐Balade, B., Verheggen, C., Molle, D., Boireau, S., Georgieva, M., Azzag, K., Robert, M.-C., Ahmad, Y., Neel, H., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.08.023 · Cited by 289 · see citing works
hORFeome v3.1: A resource of human open reading frames representing over 10,000 human genes
Lamesch, P., Li, N., Milstein, S., Fan, C., Hao, T., Szabo, G., Hu, Z., Venkatesan, K., Bethel, G., Martin, P., et al. (2007) · Genomics · doi:10.1016/j.ygeno.2006.11.012 · Cited by 272 · see citing works
Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons
Specchia, V., Piacentini, L., Tritto, P., Fanti, L., D’Alessandro, R., Palumbo, G., Pimpinelli, S., & Bozzetti, M. P. (2010) · Nature · doi:10.1038/nature08739 · Cited by 263 · see citing works
p50cdc37 Acting in Concert with Hsp90 Is Required for Raf-1 Function
Grammatikakis, N., Lin, J.-H., Grammatikakis, A., Tsichlis, P. N., & Cochran, B. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1661 · Cited by 262 · see citing works
Dias, S. D. R., Friedlos, F., Light, Y., Springer, C. J., Workman, P., & Marais, R. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2632 · Cited by 246 · see citing works
Influence of conservation on calculations of amino acid covariance in multiple sequence alignments
Fodor, A. A., & Aldrich, R. W. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20098 · Cited by 238 · see citing works
Ying, W., Du, Z., Sun, L., Foley, K. P., Proia, D. A., Blackman, R. K., Zhou, D., Inoue, T., Tatsuta, N., Sang, J., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0755 · Cited by 230 · see citing works
Hsp90 Recognizes a Common Surface on Client Kinases
Citri, A., Harari, D., Shohat-Ophir, G., Ramakrishnan, P., Gan, J., Lavi, S., Eisenstein, M., Kimchi, A., Wallach, D., Pietrokovski, S., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512613200 · Cited by 222 · see citing works
High yield bacterial expression of active c‐Abl and c‐Src tyrosine kinases
Seeliger, M. A., Young, M. A., Henderson, M. N., Pellicena, P., King, D., Falick, A. M., & Kuriyan, J. (2005) · Protein Science · doi:10.1110/ps.051750905 · Cited by 220 · see citing works
Chaperoning steroid hormone action
Picard, D. (2006) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2006.06.003 · Cited by 186 · see citing works
Molecular chaperones and protein kinase quality control
Caplan, A. J., Mandal, A. K., & Theodoraki, M. A. (2006) · Trends in Cell Biology · doi:10.1016/j.tcb.2006.12.002 · Cited by 185 · see citing works
Xu, Y., Singer, M. A., & Lindquist, S. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.109 · Cited by 184 · see citing works
Self-citationNLR sensors meet at the SGT1–HSP90 crossroad
Kadota, Y., Shirasu, K., & Guérois, R. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.12.005 · Cited by 181 · see citing works
Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex
Xu, W., Yuan, X., Xiang, Z., Mimnaugh, E. G., Marcu, M. G., & Neckers, L. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb885 · Cited by 152 · see citing works
The Hsp90 Chaperone Machinery Regulates Signaling by Modulating Ligand Binding Clefts
Pratt, W. B., Morishima, Y., & Osawa, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800023200 · Cited by 151 · see citing works
Conserved Conformational Changes in the ATPase Cycle of Human Hsp90
Richter, K., Soroka, J., Skalniak, Ł., Leskovar, A., Heßling, M., Reinstein, J., & Büchner, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800540200 · Cited by 145 · see citing works
The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology
Manning, G., Reiner, D. S., Lauwaet, T., Dacre, M., Smith, A. J., Zhai, Y., Svärd, S. G., & Gillin, F. D. (2011) · Genome biology · doi:10.1186/gb-2011-12-7-r66 · Cited by 145 · see citing works
Targeting the oncogene and kinome chaperone CDC37
Gray, P. J., Prince, T. L., Cheng, J., Stevenson, M. A., & Calderwood, S. K. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2420 · Cited by 136 · see citing works
Regulation of Hsp90 client proteins by a Cullin5-RING E3 ubiquitin ligase
Ehrlich, E. S., Wang, T., Luo, K., Xiao, Z., Niewiadomska, A. M., Martinez, T. L., Xu, W., Neckers, L., & Yu, X.-F. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810571106 · Cited by 131 · see citing works
Yang, J., Campobasso, N., Biju, M. P., Fisher, K. E., Pan, X.-Q., Cottom, J., Galbraith, S., Ho, T. F., Zhang, H., Hong, X., et al. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.12.013 · Cited by 113 · see citing works
Mandal, A. K., Lee, P. C., Chen, J. A., Nillegoda, N. B., Heller, A., DiStasio, S., Oen, H. O., Victor, J., Nair, D. M., Brodsky, J. L., et al. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200604106 · Cited by 104 · see citing works
A proteomic snapshot of the human heat shock protein 90 interactome
Falsone, S. F., Gesslbauer, B., Tirk, F., Piccinini, A. M., & Kungl, A. J. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.10.020 · Cited by 97 · see citing works
Allosteric Interactions between the Myristate- and ATP-Site of the Abl Kinase
Iacob, R. E., Zhang, J., Gray, N. S., & Engen, J. R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015929 · Cited by 73 · see citing works
Ricketson, D., Hostick, U., Fang, L., Yamamoto, K. R., & Darimont, B. D. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.02.057 · Cited by 69 · see citing works
Ghosh, A., Chawla‐Sarkar, M., & Stuehr, D. J. (2011) · The FASEB Journal · doi:10.1096/fj.10-180554 · Cited by 68 · see citing works
Oncogenic Mutations Reduce the Stability of Src Kinase
Falsone, S. F., Leptihn, S., Osterauer, A., Haslbeck, M., & Büchner, J. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.08.091 · Cited by 51 · see citing works
Mutational Activation of ErbB2 Reveals a New Protein Kinase Autoinhibition Mechanism
Fan, Y., Wong, L., Ding, J., Spiridonov, N. A., Johnson, R. C., & Johnson, G. R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708116200 · Cited by 47 · see citing works
Bacterial Hsp90 - desperately seeking clients
Büchner, J. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07140.x · Cited by 32 · see citing works
A proteomic approach towards the Hsp90‐dependent ubiquitinylated proteome
Falsone, S. F., Gesslbauer, B., Rek, A., & Kungl, A. J. (2007) · PROTEOMICS · doi:10.1002/pmic.200600996 · Cited by 31 · see citing works
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Schopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540 · see citing works
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486 · see citing works
In vivo aspects of protein folding and quality control
Balchin, D., Hayer-Hartl, M. K., & Hartl, F. U. (2016) · Science · doi:10.1126/science.aac4354 · Cited by 1,432 · see citing works
Lu, H., Zhou, Q., He, J., Jiang, Z., Peng, C., Tong, R., & Shi, J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00315-3 · Cited by 891 · see citing works
Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities
Hu, C., Yang, J. C., Qi, Z., Wu, H., Wang, B., Zou, F., Mei, H., Liu, J. L., Wang, W., & Liu, Q. (2022) · MedComm · doi:10.1002/mco2.161 · Cited by 811 · see citing works
Antifungal Drug Resistance: Molecular Mechanisms in <i>Candida albicans</i> and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801 · see citing works
Pathways of cellular proteostasis in aging and disease
Klaips, C. L., Jayaraj, G. G., & Hartl, F. U. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201709072 · Cited by 801 · see citing works
The heat‐shock protein/chaperone network and multiple stress resistance
Jacob, P., Heribert Hirt, A., & Bendahmane, A. (2016) · Plant Biotechnology Journal · doi:10.1111/pbi.12659 · Cited by 766 · see citing works
An atlas of substrate specificities for the human serine/threonine kinome
Johnson, J. L., Yaron, T. M., Huntsman, E. M., Kerelsky, A., Song, J., Regev, A., Lin, T.-Y., Liberatore, K., Cizin, D. M., Cohen, B. M., et al. (2023) · Nature · doi:10.1038/s41586-022-05575-3 · Cited by 728 · see citing works
Widespread macromolecular interaction perturbations in human genetic disorders
Sahni, N., Yi, S., Taipale, M., Fuxman Bass, J. I., Coulombe-Huntington, J., Yang, F., Peng, J., Weile, J., Karras, G. I., Wang, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.013 · Cited by 594 · see citing works
Self-citationMAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway
Meng, Z., Moroishi, T., Mottier, V., Plouffe, S. W., Hansen, C. G., Hong, A. W., Park, H. W., Mo, J., Lü, W., Lu, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms9357 · Cited by 524 · see citing works
Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase
Verba, K. A., Wang, R. Y.-R., Arakawa, A., Liu, Y., Shirouzu, M., Yokoyama, S., & Agard, D. A. (2016) · Science · doi:10.1126/science.aaf5023 · Cited by 424 · see citing works
Taipale, M., Tucker, G., Peng, J., Krykbaeva, I., Lin, Z., Larsen, B. G., Choi, H., Berger, B., Gingras, A., & Lindquist, S. L. (2014) · Cell · doi:10.1016/j.cell.2014.05.039 · Cited by 388 · see citing works
Self-citationHsp90 and Hsp70 chaperones: Collaborators in protein remodeling
Genest, O., Wickner, S., & Doyle, S. M. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.rev118.002806 · Cited by 384 · see citing works
Determinants of the rate of protein sequence evolution
Zhang, J., & Yang, J. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3950 · Cited by 361 · see citing works
Cryptic Variation in Morphological Evolution: HSP90 as a Capacitor for Loss of Eyes in Cavefish
Rohner, N., Jarosz, D. F., Kowalko, J. E., Yoshizawa, M., Jeffery, W. R., Borowsky, R. L., Lindquist, S., & Tabin, C. J. (2013) · Science · doi:10.1126/science.1240276 · Cited by 353 · see citing works
Self-citationWidespread Regulation of Translation by Elongation Pausing in Heat Shock
Shalgi, R., Hurt, J. A., Krykbaeva, I., Taipale, M., Lindquist, S. L., & Burge, C. B. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.11.028 · Cited by 334 · see citing works
Self-citationFitness Trade-offs Restrict the Evolution of Resistance to Amphotericin B
Vincent, B. M., Lancaster, A. K., Scherz-Shouval, R., Whitesell, L., & Lindquist, S. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001692 · Cited by 322 · see citing works
Self-citationPervasive robustness in biological systems
Félix, M., & Barkoulas, M. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3949 · Cited by 319 · see citing works
Lambert, J.-P., Ivosev, G., Couzens, A. L., Larsen, B., Taipale, M., Lin, Z.-Y., Zhong, Q., Lindquist, S., Vidal, M., Aebersold, R., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2702 · Cited by 318 · see citing works
Self-citationHsp90-Tau complex reveals molecular basis for specificity in chaperone action
Karagöz, G. E., Duarte, A. M. S., Akoury, E., Ippel, H., Biernat, J., Morán Luengo, T., Radli, M., Didenko, T., Nordhues, B. A., Veprintsev, D. B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.01.037 · Cited by 318 · see citing works
“The substrate pool of Hsp90 does not share a common sequence or structural motif (Taipale et al., 2010, 2012).”
Structure, Function, and Regulation of the Hsp90 MachineryPreprint
Biebl, M. M., & Büchner, J. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034017 · Cited by 308 · see citing works
The Hsp70–Hsp90 Chaperone Cascade in Protein Folding
Luengo, T. M., Mayer, M. P., & Rüdiger, S. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.10.004 · Cited by 276 · see citing works
Wang, R., Zhang, Y., Kieffer, M., Yu, H. J., Kepinski, S., & Estelle, M. A. (2016) · Nature Communications · doi:10.1038/ncomms10269 · Cited by 270 · see citing works
The Ribosome as a Hub for Protein Quality Control
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The chaperone Hsp90: changing partners for demanding clients
Röhl, A., Rohrberg, J., & Büchner, J. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.02.003 · Cited by 268 · see citing works
Evolution of heat‐shock protein expression underlying adaptive responses to environmental stress
Chen, B., Feder, M. E., & Kang, L. (2018) · Molecular Ecology · doi:10.1111/mec.14769 · Cited by 267 · see citing works
An efficient KRAB domain for CRISPRi applications in human cells
Alerasool, N., Segal, D., Lee, H., & Taipale, M. (2020) · Nature Methods · doi:10.1038/s41592-020-0966-x · Cited by 265 · see citing works
Self-citationStructural insights into the functional diversity of the CDK–cyclin family
Wood, D. J., & Endicott, J. (2018) · Open Biology · doi:10.1098/rsob.180112 · Cited by 264 · see citing works
Functional Modules of the Proteostasis NetworkPreprint
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Targeted protein degradation for cancer therapy
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Hsp90, an unlikely ally in the war on cancer
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Savitski, M. M., Zinn, N., Faelth-Savitski, M., Poeckel, D., Gade, S., Becher, I., Muelbaier, M., Wagner, A. J., Strohmer, K., Werner, T., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.030 · Cited by 217 · see citing works
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Karagöz, G. E., & Rüdiger, S. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.12.002 · Cited by 203 · see citing works
Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells
Hergueta‐Redondo, M., Sarrió, D., Molina-Crespo, Á., Megı́as, D., Mota, A., Rojo‐Sebastián, A., García‐Sanz, P., Morales, S., Abril, S., Cano, A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090099 · Cited by 197 · see citing works
Nebenfuehr, S., Kollmann, K., & Sexl, V. (2020) · International Journal of Cancer · doi:10.1002/ijc.33054 · Cited by 185 · see citing works
HSP90AB1: Helping the good and the bad
Haase, M., & Fitze, G. (2016) · Gene · doi:10.1016/j.gene.2015.08.063 · Cited by 179 · see citing works
Mayer, M. P., & Breton, L. L. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.022 · Cited by 176 · see citing works
Schmidt, F. I., Lu, A. Z., Chen, J. W., Ruan, J., Tang, C., Wu, H., & Ploegh, H. L. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151790 · Cited by 173 · see citing works
Review: The HSP90 molecular chaperone—an enigmatic ATPase
Pearl, L. H. (2016) · Biopolymers · doi:10.1002/bip.22835 · Cited by 172 · see citing works
Petschnigg, J., Groisman, B., Kotlyar, M., Taipale, M., Zheng, Y., Kurat, C. F., Sayad, A., Sierra, J. R., Ušaj, M. M., Snider, J. D., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2895 · Cited by 171 · see citing works
Self-citationThe eNOS signalosome and its link to endothelial dysfunction
Siragusa, M., & Fleming, I. (2016) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-016-1839-0 · Cited by 171 · see citing works
Site-specific proteasome phosphorylation controls cell proliferation and tumorigenesis.
Guo, X., Wang, X., Wang, Z., Banerjee, S., Yang, J., Huang, L., & Dixon, J. E. (2016) · Nature Cell Biology · doi:10.1038/ncb3289 · Cited by 169 · see citing works
Role of Heat Shock Proteins (HSP70 and HSP90) in Viral Infection
Lubkowska, A., Pluta, W. W., Strońska-Pluta, A., & Lalko, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179366 · Cited by 168 · see citing works
Fries, G. R., Gassen, N. C., & Rein, T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122614 · Cited by 167 · see citing works
Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism
Noddings, C. M., Wang, R. Y.-R., Johnson, J. L., & Agard, D. A. (2022) · Nature · doi:10.1038/s41586-021-04236-1 · Cited by 165 · see citing works
Lang, B. J., Guerrero-Gimenez, M. E., Prince, T. L., Okusha, Y., Bonorino, C., & Calderwood, S. K. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-03070-8 · Cited by 165 · see citing works
Epithelial-derived gasdermin D mediates nonlytic IL-1β release during experimental colitis
Bulek, K., Zhao, J., Liao, Y., Rana, N., Corridoni, D., Antanaviciute, A., Chen, X., Wang, H., Wen, Q., Miller-Little, W. A., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci138103 · Cited by 161 · see citing works
Jacobsen, A. V., Lowes, K. N., Tanzer, M. C., Lucet, I. S., Hildebrand, J. M., Petrie, E. J., van Delft, M. F., Liu, Z., Conos, S. A., Zhang, J.-G., et al. (2016) · Cell Death & Disease · doi:10.1038/cddis.2015.386 · Cited by 160 · see citing works
Landscape of the mitochondrial Hsp90 metabolome in tumours
Chae, Y. C., Angelin, A., Lisanti, S., Kossenkov, A. V., Speicher, K. D., Wang, H., Powers, J. F., Tischler, A. S., Pacák, K., Fliedner, S. M. J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3139 · Cited by 158 · see citing works
Lavery, L. A., Partridge, J. R., Ramelot, T. A., Elnatan, D., Kennedy, M. A., & Agard, D. A. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.023 · Cited by 158 · see citing works
Jasmonate signalling in Arabidopsis involves SGT1b–HSP70–HSP90 chaperone complexes
Zhang, X.-C., Millet, Y. A., Cheng, Z., Bush, J., & Ausubel, F. M. (2015) · Nature Plants · doi:10.1038/nplants.2015.49 · Cited by 154 · see citing works
Kijima, T., Prince, T. L., Tigue, M. L., Yim, K. H., Schwartz, H., Beebe, K. E., Lee, S., Budzyński, M. A., Williams, H., Trepel, J. B., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-25404-w · Cited by 154 · see citing works
Modulation of the Hsp90 Chaperone Cycle by a Stringent Client Protein
Lorenz, O. R., Freiburger, L., Rutz, D. A., Krause, M., Zierer, B. K., Alvira, S., Cuéllar, J., Valpuesta, J. M., Madl, T., Sattler, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.02.003 · Cited by 151 · see citing works
Gedunin Inactivates the Co-chaperone p23 Protein Causing Cancer Cell Death by Apoptosis
Patwardhan, C. A., Fauq, A. H., Peterson, L. B., Miller, C. A., Blagg, B. S. J., & Chadli, A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.427328 · Cited by 151 · see citing works
Hsp90 Breaks the Deadlock of the Hsp70 Chaperone System
Luengo, T. M., Kityk, R., Mayer, M. P., & Rüdiger, S. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.028 · Cited by 151 · see citing works
The intrinsic substrate specificity of the human tyrosine kinome
Yaron, T. M., Joughin, B. A., Huntsman, E. M., Kerelsky, A., Cizin, D. M., Cohen, B. M., Regev, A., Song, J., Vasan, N., Lin, T.-Y., et al. (2024) · Nature · doi:10.1038/s41586-024-07407-y · Cited by 151 · see citing works
Cha, J., Kim, J., Kim, T.-S., Zeng, Q., Wang, L., Lee, S. Y., Kim, W.-Y., & Somers, D. (2017) · Nature Communications · doi:10.1038/s41467-016-0014-9 · Cited by 126 · see citing works
Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells
Vihervaara, A., Sergelius, C., Vasara, J., Blom, M. A. H., Elsing, A. N., Roos‐Mattjus, P., & Sistonen, L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305275110 · Cited by 149 · see citing works
Anticancer Inhibitors of Hsp90 Function
Garg, G., Khandelwal, A., & Blagg, B. S. J. (2016) · Advances in cancer research · doi:10.1016/bs.acr.2015.12.001 · Cited by 147 · see citing works
Identification of Protein Interactions Involved in Cellular Signaling
Westermarck, J., Ivaska, J., & Corthals, G. L. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r113.027771 · Cited by 143 · see citing works
ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system
Polier, S., Samant, R. S., Clarke, P. A., Workman, P., Prodromou, C., & Pearl, L. H. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1212 · Cited by 140 · see citing works
Bhattacharya, K., Weidenauer, L., Luengo, T. M., Pieters, E. C., Echeverría, P. C., Bernasconi, L., Wider, D., Sadian, Y., Koopman, M. B., Villemin, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19783-w · Cited by 140 · see citing works
Chaperoning Endoplasmic Reticulum–Associated Degradation (ERAD) and Protein Conformational DiseasesPreprint
Needham, P. G., Guerriero, C. J., & Brodsky, J. L. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033928 · Cited by 139 · see citing works
The Plasticity of the Hsp90 Co-chaperone System
Sahasrabudhe, P., Rohrberg, J., Biebl, M. M., Rutz, D. A., & Buchner, J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.004 · Cited by 136 · see citing works
Leach, M. D., Budge, S., Walker, L. A., Munro, C. A., Cowen, L. E., & Brown, A. J. P. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003069 · Cited by 133 · see citing works
Urbanus, M. L., Quaile, A. T., Stogios, P. J., Morar, M., Rao, C., Leo, R. D., Evdokimova, E., Lam, M. H. Y., Oatway, C., Cuff, M. E., et al. (2016) · Molecular Systems Biology · doi:10.15252/msb.20167381 · Cited by 129 · see citing works
Self-citationHSP90 Shapes the Consequences of Human Genetic Variation
Karras, G. I., Yi, S. S., Sahni, N., Fischer, M., Xie, J., Vidal, M., D’Andrea, A. D., Whitesell, L. J., & Lindquist, S. L. (2017) · Cell · doi:10.1016/j.cell.2017.01.023 · Cited by 129 · see citing works
Self-citationTaipale, M., Krykbaeva, I., Whitesell, L. J., Santagata, S., Zhang, J., Liu, Q., Gray, N. S., & Lindquist, S. L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2620 · Cited by 128 · see citing works
Self-citationHSF1 deficiency and impaired HSP90‐dependent protein folding are hallmarks of aneuploid human cells
Donnelly, N., Passerini, V., Dürrbaum, M., Stingele, S., & Štorchová, Z. (2014) · The EMBO Journal · doi:10.15252/embj.201488648 · Cited by 126 · see citing works
DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging
Park, S. J., Gavrilova, O., Brown, A. L., Soto, J. E., Bremner, S. N., Kim, J., Xu, X., Yang, S., Um, J.-H., Koch, L. G., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.008 · Cited by 123 · see citing works
Alvira, S., Cuéllar, J., Röhl, A., Yamamoto, S., Itoh, H., Alfonso, C., Rivas, G., Büchner, J., & Valpuesta, J. (2014) · Nature Communications · doi:10.1038/ncomms6484 · Cited by 121 · see citing works
HSP90 mediates the connection of multiple programmed cell death in diseases
Peng, C., Zhao, F., Li, H., Li, L., Yang, Y., & Liu, F. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05373-9 · Cited by 120 · see citing works
Identification and functional characterization of transcriptional activators in human cells
Alerasool, N., Leng, H., Lin, Z.-Y., Gingras, A.-C., & Taipale, M. (2022) · Molecular Cell · doi:10.1016/j.molcel.2021.12.008 · Cited by 120 · see citing works
Self-citationHSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models
Whitesell, L. J., Santagata, S., Mendillo, M. L., Lin, N., Proia, D. A., & Lindquist, S. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421323111 · Cited by 119 · see citing works
Self-citationSolvent-Induced Protein Precipitation for Drug Target Discovery on the Proteomic Scale
Zhang, X., Wang, Q., Li, Y., Ruan, C., Wang, S., Hu, L., & Ye, M. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b04531 · Cited by 119 · see citing works
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases
Buljan, M., Ciuffa, R., van Drogen, A., Vichalkovski, A., Mehnert, M., Rosenberger, G., Lee, S., Varjosalo, M. T., Pernas, L. E., Spegg, V., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.07.001 · Cited by 115 · see citing works
Redundancy, Feedback, and Robustness in the Arabidopsis thaliana BZR/BEH Gene Family
Lachowiec, J., Mason, G. A., Schultz, K., & Queitsch, C. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00523 · Cited by 112 · see citing works
Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer
Wang, L., Zhang, L., Li, L., Jiang, J., Zheng, Z., Shang, J., Wang, C., Chen, W., Bao, Q., Xu, X., et al. (2019) · Science Advances · doi:10.1126/sciadv.aax2277 · Cited by 110 · see citing works
Folding or holding?—Hsp70 and Hsp90 chaperoning of misfolded proteins in neurodegenerative disease
Rutledge, B. S., Choy, W., & Duennwald, M. L. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101905 · Cited by 110 · see citing works
Jahn, M., Rehn, A., Pelz, B., Hellenkamp, B., Richter, K., Rief, M., Büchner, J., & Hugel, T. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414073111 · Cited by 110 · see citing works
Proteome Instability Is a Therapeutic Vulnerability in Mismatch Repair-Deficient Cancer
McGrail, D. J., Garnett, J., Yin, J., Dai, H., Shih, D. J. H., Lam, T., Li, Y., Sun, C., Li, Y., Schmandt, R. E., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.01.011 · Cited by 108 · see citing works
The Roles of NDR Protein Kinases in Hippo Signalling
Hergovich, A. (2016) · Genes · doi:10.3390/genes7050021 · Cited by 105 · see citing works
Condelli, V., Crispo, F., Pietrafesa, M., Lettini, G., Matassa, D. S., Esposito, F., Landriscina, M., & Maddalena, F. (2019) · Cells · doi:10.3390/cells8060532 · Cited by 105 · see citing works
Samakovli, D., Tichá, T., Vavrdová, T., Ovečka, M., Luptovčiak, I., Zapletalová, V., Kuchařová, A., Křenek, P., Krasylenko, Y. A., Margaritopoulou, T., et al. (2020) · Molecular Plant · doi:10.1016/j.molp.2020.01.001 · Cited by 105 · see citing works
The Chemical Biology of Molecular Chaperones—Implications for Modulation of Proteostasis
Brandvold, K. R., & Morimoto, R. I. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.05.010 · Cited by 105 · see citing works
Ayaz, P., Lyczek, A., Paung, Y., Mingione, V. R., Iacob, R. E., de Waal, P. W., Engen, J. R., Seeliger, M. A., Shan, Y., & Shaw, D. E. (2023) · Nature Communications · doi:10.1038/s41467-023-36956-5 · Cited by 105 · see citing works
Nicolae, C. M., Aho, E. R., Vlahos, A. H. S., Choe, K. N., De, S., Karras, G. I., & Moldovan, G. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.556340 · Cited by 104 · see citing works
Self-citationDancing with the Diva: Hsp90–Client Interactions
Radli, M., & Rüdiger, S. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.05.026 · Cited by 101 · see citing works
How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches
Verba, K. A., & Agard, D. A. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.07.002 · Cited by 98 · see citing works
Serwetnyk, M. A., & Blagg, B. S. J. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.015 · Cited by 97 · see citing works
The role of cullin 5-containing ubiquitin ligases
Okumura, F., Akiko, J.-O., Nakatsukasa, K., & Kamura, T. (2016) · Cell Division · doi:10.1186/s13008-016-0016-3 · Cited by 96 · see citing works
Structures of Large Protein Complexes Determined by Nuclear Magnetic Resonance Spectroscopy
Huang, C., & Kalodimos, C. G. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-070816-033701 · Cited by 96 · see citing works
GP96 is a GARP chaperone and controls regulatory T cell functions
Zhang, Y., Wu, B. X., Metelli, A., Thaxton, J. E., Hong, F., Rachidi, S., Ansa-Addo, E., Sun, S., Vasu, C., Yang, Y., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79014 · Cited by 95 · see citing works
Foulkes, D. M., Byrne, D. P., Yeung, W., Shrestha, S., Bailey, F. P., Ferries, S., Eyers, C. E., Keeshan, K., Wells, C. I., Drewry, D. H., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aat7951 · Cited by 94 · see citing works
The fungal Achilles’ heel: targeting Hsp90 to cripple fungal pathogens
Cowen, L. E. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.03.005 · Cited by 93 · see citing works
Comparing protein folding in vitro and in vivo: foldability meets the fitness challenge
Hingorani, K. S., & Gierasch, L. M. (2014) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2013.11.007 · Cited by 93 · see citing works
The Hsp90 chaperone network modulates Candida virulence traits
O’Meara, T. R., Robbins, N., & Cowen, L. E. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.05.003 · Cited by 92 · see citing works
Dahiya, V., Agam, G. N., Lawatscheck, J., Rutz, D. A., Lamb, D. C., & Büchner, J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.03.026 · Cited by 92 · see citing works
- Authors
- Taipale, M., Krykbaeva, I., Koeva, M., Kayatekin, C., Westover, K. D., Karras, G. I., & Lindquist, S.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lindquist, Susan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 150
- Issue
- 5
- Pages
- 987-1001
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3894786
- OpenAlex
- W2096237314
- Cited by
- 879
- References
- 47
- Citations by year
- 2026: 49 · 2025: 59 · 2024: 59 · 2023: 61 · 2022: 55 · 2021: 48 · 2020: 78 · 2019: 55 · 2018: 77 · 2017: 59 · 2016: 70 · 2015: 72 · 2014: 75 · 2013: 53 · 2012: 6
- FWCI
- 26.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Elsevier eBooks
- Funders
- Howard Hughes Medical Institute
- National Human Genome Research Institute (RL1HG004671)
- National Cancer Institute (RL1CA133834)
- National Institute of General Medical Sciences (RL1GM084437)
- National Institute of Dental and Craniofacial Research (UL1DE019585)
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- HSP90, Hsp90 client proteins, Cdc37, molecular chaperones, substrate recognition, protein-protein interaction, kinases, transcription factors, E3 ubiquitin ligase, small molecule inhibitors, binding thermodynamics
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Models, Molecular, Molecular Sequence Data, Protein Kinases, Receptors, Steroid, Thermodynamics, Transcription Factors, Sequence Alignment, Cell Cycle Proteins, Chaperonins, HSP90 Heat-Shock Proteins, Proteome, Protein Interaction Mapping, Ubiquitin-Protein Ligases, Luciferases, Renilla, Protein Interaction Domains and Motifs, Protein Stability
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