p23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity
Open accessAbstract
The molecular chaperone Hsp90 assists a subset of cellular proteins and is essential in eukaryotes. A cohort of cochaperones contributes to and regulates the multicomponent Hsp90 machine. Unlike the biochemical activities of the cochaperone p23, its in vivo functions and the structure-function relationship remain poorly understood, even in the genetically tractable model organism Saccharomyces cerevisiae. The SBA1 gene that encodes the p23 ortholog in this species is not an essential gene. We found that in the absence of p23/Sba1p, yeast and mammalian cells are hypersensitive to Hsp90 inhibitors. This protective function of Sba1p depends on its abilities to bind Hsp90 and to block the Hsp90 ATPase and inhibitor binding. In contrast, the protective function of Sba1p does not require the Hsp90-independent molecular chaperone activity of Sba1p. The structure-function analysis suggests that Sba1p undergoes considerable structural rearrangements upon binding Hsp90 and that the large size of the p23/Sba1p-Hsp90 interaction surface facilitates maintenance of high affinity despite sequence divergence during evolution. The large interface may also contribute to preserving a protective function in an environment in which Hsp90 inhibitory compounds can be produced by various microorganisms.
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The difference in in vitro ATPase IC50 is not sufficient alone to explain the cellular-level observation because in vivo Hsp90 ATPase activity is regulated by cochaperones.
“However, since in vivo ATPase activity of Hsp90 is known to be regulated by many cochaperones which either stimulate or bring down Hsp90 ATPase activity, the difference in ATPase IC50 observed in vitro is not sufficient alone to explain the observation at the cellular level.”
From Heat shock protein 90 localizes to the surface and augments virulence factors of Cryptococcus neoformans (2017) · cites this paper as [30]
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SWISS-MODEL: an automated protein homology-modeling server
Schwede, T. F. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg520 · Cited by 5,592 · see citing works
Brachmann, C. B., Davies, A., Cost, G. J., Caputo, E. M., Li, J., Hieter, P., & Boeke, J. D. (1998) · Yeast · doi:10.1002/(sici)1097-0061(19980130)14:2 · Cited by 3,411 · see citing works
HSP90 and the chaperoning of cancer
Whitesell, L., & Lindquist, S. L. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1716 · Cited by 2,502 · see citing works
A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors
Kamal, A., Thao, L., Sensintaffar, J., Zhang, L., Boehm, M. F., Fritz, L. C., & Burrows, F. J. (2003) · Nature · doi:10.1038/nature01913 · Cited by 1,380 · see citing works
Structure and mechanism of the Hsp90 molecular chaperone machinery
Pearl, L. H., & Prodromou, C. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142738 · Cited by 1,103 · see citing works
Crystal structure of an Hsp90–nucleotide–p23/Sba1 closed chaperone complex
Ali, M. M. U., Roe, S. M., Vaughan, C. K., Meyer, P., Panaretou, B., Piper, P. W., Prodromou, C., & Pearl, L. H. (2006) · Nature · doi:10.1038/nature04716 · Cited by 962 · cited 6× · see citing works
“A13, Q14, R15, K113, and Y116 are all localized in the large interface that packs against the lid of Hsp90 and consists of Sba1p residues 13 to 16 and 113 to 118 (2), and yet only A13S and K113A have slightly reduced Hsp90 binding both in vitro and in IP experiments performed under certain conditions.”
BackgroundInfluentialZhao, R., Davey, M., Hsu, Y.-C., Kaplanek, P., Tong, A., Parsons, A. B., Krogan, N., Cagney, G., Mai, D., Greenblatt, J., et al. (2005) · Cell · doi:10.1016/j.cell.2004.12.024 · Cited by 819 · see citing works
Heat-shock protein 90, a chaperone for folding and regulation
Picard, D. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/pl00012491 · Cited by 797 · see citing works
ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo
Panaretou, B., Prodromou, C., Roe, S. M., O'Brien, R., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1998) · The EMBO Journal · doi:10.1093/emboj/17.16.4829 · Cited by 735 · see citing works
Exploring the Mode-of-Action of Bioactive Compounds by Chemical-Genetic Profiling in Yeast
Parsons, A. B., López, A., Givoni, I. E., Williams, D. E., Gray, C. A., Porter, J., Chua, G., Sopko, R., Brost, R. L., Ho, C.-H., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.040 · Cited by 500 · see citing works
Prodromou, C., Panaretou, B., Chohan, S., Siligardi, G., O'Brien, R., Ladbury, J. E., Roe, S. M., Piper, P. W., & Pearl, L. H. (2000) · The EMBO Journal · doi:10.1093/emboj/19.16.4383 · Cited by 492 · see citing works
Schulte, T. W., Blagosklonny, M. V., Ingui, C., & Neckers, L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.24585 · Cited by 457 · see citing works
Freeman, B., Myers, M. P., Schumacher, R. J., & Morimoto, R. I. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07222.x · Cited by 428 · see citing works
The glucocorticoid responses are shaped by molecular chaperones
Grad, I., & Picard, D. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.05.018 · Cited by 423 · see citing works
Self-citationDisassembly of Transcriptional Regulatory Complexes by Molecular Chaperones
Freeman, B. C., & Yamamoto, K. R. (2002) · Science · doi:10.1126/science.1073051 · Cited by 400 · see citing works
Self-citationChaperone Function of Hsp90-Associated Proteins
Bose, S., Weikl, T., Bügl, H., & Buchner, J. (1996) · Science · doi:10.1126/science.274.5293.1715 · Cited by 379 · see citing works
Freeman, B. C., Toft, D. O., & Morimoto, R. I. (1996) · Science · doi:10.1126/science.274.5293.1718 · Cited by 370 · cited 1× · see citing works
“independent molecular chaperone function, which has been described for human p23 (5, 19, 61), remains unclear.”
BackgroundAntimyeloma activity of heat shock protein-90 inhibition
Mitsiades, C. S. (2005) · Blood · doi:10.1182/blood-2005-03-1158 · Cited by 317 · see citing works
Folding of the Glucocorticoid Receptor by the Heat Shock Protein (hsp) 90-based Chaperone Machinery
Dittmar, K. D., Demady, D. R., Stancato, L., Krishna, P., & Pratt, W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.21213 · Cited by 288 · see citing works
Stimulation of the weak ATPase activity of human hsp90 by a client protein.
McLaughlin, S., Smith, H. W., & Jackson, S. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5245 · Cited by 244 · see citing works
Binding of p23 and hsp90 during assembly with the progesterone receptor.
Johnson, J. L., & Toft, D. O. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.6.8592513 · Cited by 233 · see citing works
Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle
Siligardi, G., Hu, B., Panaretou, B., Piper, P. W., Pearl, L. H., & Prodromou, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410562200 · Cited by 207 · cited 1× · see citing works
“5B), which is consistent with a stabilization of the ATP-bound form (9, 33, 52, 56).”
BackgroundCoordinated ATP Hydrolysis by the Hsp90 Dimer
Richter, K., Muschler, P., Hainzl, O., & Büchner, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103832200 · Cited by 207 · see citing works
The Co-chaperone p23 Arrests the Hsp90 ATPase Cycle to Trap Client Proteins
McLaughlin, S. H., Sobott, F., Yao, Z.-P., Zhang, W., Nielsen, P. R., Grossmann, J. G., Laue, E. D., Robinson, C. V., & Jackson, S. E. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.11.085 · Cited by 196 · cited 1× · see citing works
“5B), which is consistent with a stabilization of the ATP-bound form (9, 33, 52, 56).”
BackgroundChaperoning 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
Freeman, B. C., Felts, S. J., Toft, D. O., & Yamamoto, K. R. (2000) · Genes & Development · doi:10.1101/gad.14.4.422 · Cited by 168 · see citing works
Richter, K., Walter, S., & Buchner, J. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.07.064 · Cited by 159 · cited 2× · see citing works
“5B), which is consistent with a stabilization of the ATP-bound form (9, 33, 52, 56).”
BackgroundMethodSBA1 Encodes a Yeast Hsp90 Cochaperone That Is Homologous to Vertebrate p23 Proteins
Fang, Y., Fliss, A., Rao, J., & Caplan, A. J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.3727 · Cited by 154 · see citing works
A Rhizosphere Fungus Enhances Arabidopsis Thermotolerance through Production of an HSP90 Inhibitor
McLellan, C. A., Turbyville, T. J., Wijeratne, E. M. K., Kerschen, A., Vierling, E., Queitsch, C., Whitesell, L. J., & Gunatilaka, A. A. L. (2007) · PLANT PHYSIOLOGY · doi:10.1104/pp.107.101808 · Cited by 144 · see citing works
Crystal Structure and Activity of Human p23, a Heat Shock Protein 90 Co-chaperone
Weaver, A. J., Sullivan, W. P., Felts, S. J., Owen, B. A. L., & Toft, D. O. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003410200 · Cited by 136 · see citing works
The Hsp90 chaperone complex is both a facilitator and a repressor of the dsRNA‐dependent kinase PKR
Donzé, O., Abbas‐Terki, T., & Picard, D. (2001) · The EMBO Journal · doi:10.1093/emboj/20.14.3771 · Cited by 126 · see citing works
Role for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction
Knoblauch, R., & Garabedian, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3748 · Cited by 126 · see citing works
Gooljarsingh, L. T., Fernandes, C., Yan, K., Zhang, H., Grooms, M. H., Johanson, K., Sinnamon, R. H., Kirkpatrick, R. B., Kerrigan, J. J., Lewis, T. S., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602650103 · Cited by 116 · see citing works
p23, a simple protein with complex activities
Felts, S. J., & Toft, D. O. (2003) · Cell Stress and Chaperones · doi:10.1379/1466-1268(2003)008 · Cited by 116 · see citing works
Louvion, J.-F., Warth, R., & Picard, D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13937 · Cited by 113 · see citing works
Ouspenski, I. I., Elledge, S. J., & Brinkley, B. R. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.15.3001 · Cited by 113 · see citing works
Independent Regulation of Hsp70 and Hsp90 Chaperones by Hsp70/Hsp90-organizing Protein Sti1 (Hop1)
Song, Y., & Masison, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505420200 · Cited by 112 · see citing works
The Influence of ATP and p23 on the Conformation of hsp90
Sullivan, W. P., Owen, B. A. L., & Toft, D. O. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207754200 · Cited by 111 · cited 1× · see citing works
“This suggests that the binding of Sba1p to the Hsp90-ATP complex might protect Hsp90 from binding an inhibitor molecule, which is compatible with the tight and intimate nature of the ternary complex (2) and the ability of human p23 to stabilize the nucleotide-bound state of Hsp90 (58).”
BackgroundBohen, S. P. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.6.3330 · Cited by 106 · see citing works
Bandhakavi, S., McCann, R. O., Hanna, D. E., & Glover, C. V. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206662200 · Cited by 101 · see citing works
Weikl, T., Abelmann, K., & Buchner, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3172 · Cited by 97 · cited 3× · see citing works
“This mutant lacks the poorly conserved and apparently unstructured, highly acidic tail, which may carry or contribute to the chaperone activity (60, 61).”
BackgroundResultHsp104 Interacts with Hsp90 Cochaperones in Respiring Yeast
Abbas‐Terki, T., Donzé, O., Briand, P.-A., & Picard, D. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.22.7569-7575.2001 · Cited by 94 · see citing works
The Hsp90 Cochaperone p23 Is Essential for Perinatal Survival
Grad, I., McKee, T., Ludwig, S. M., Hoyle, G. W., Ruíz, P., Wurst, W., Floß, T., Miller, C. A., & Picard, D. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00734-06 · Cited by 91 · see citing works
Cooperation of heat shock protein 90 and p23 in aryl hydrocarbon receptor signaling
Cox, M., & Miller, C. A. (2004) · Cell stress & chaperones (Print) · doi:10.1379/1466-1268(2004)009 · Cited by 90 · see citing works
Dolinski, K. J., Cardenas, M. E., & Heitman, J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.12.7344 · Cited by 87 · see citing works
Lovgren, A. K., Kovářová, M., & Koller, B. H. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02314-06 · Cited by 81 · see citing works
The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes
Johnson, J. L., Corbisier, R., Stensgard, B. A., & Toft, D. O. (1996) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(95)00221-9 · Cited by 79 · see citing works
Donzé, O., & Picard, D. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.12.8422 · Cited by 79 · see citing works
Johnson, J. L., Halaś, A., & Flom, G. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01034-06 · Cited by 76 · see citing works
Piper, P. W., Millson, S. H., Mollapour, M., Panaretou, B., Siligardi, G., Pearl, L. H., & Prodromou, C. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03866.x · Cited by 64 · see citing works
ALG-2: a Ca2+-binding modulator protein involved in cell proliferation and in cell death
Krebs, J. J. R., Saremaslani, P., & Caduff, R. F. (2002) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/s1570-9639(02)00446-6 · Cited by 58 · see citing works
The p23 molecular chaperone promotes functional telomerase complexes through DNA dissociation
Toogun, O. A., Zeiger, W., & Freeman, B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701442104 · Cited by 54 · see citing works
Heat Shock Protein 90: A Unique Chemotherapeutic Target
Cullinan, S. B., & Whitesell, L. J. (2006) · Seminars in Oncology · doi:10.1053/j.seminoncol.2006.04.001 · Cited by 54 · see citing works
Oxelmark, E., Roth, J., Brooks, P., Braunstein, S., Schneider, R., & Garabedian, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00009-06 · Cited by 53 · see citing works
Piper, P. W., Panaretou, B., Millson, S. H., Trumana, A., Mollapour, M., Pearl, L. H., & Prodromou, C. (2003) · Gene · doi:10.1016/s0378-1119(02)01102-2 · Cited by 53 · see citing works
Inhibition of GR‐mediated transcription by p23 requires interaction with Hsp90
Wochnik, G. M., Young, J. C., Schmidt, U., Holsboer, F., Hartl, F. U., & Rein, T. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00066-3 · Cited by 46 · see citing works
The p23 co-chaperone facilitates dioxin receptor signaling in a yeast model system
Cox, M. B., & Miller, C. A. (2002) · Toxicology Letters · doi:10.1016/s0378-4274(01)00465-9 · Cited by 43 · see citing works
Muñoz, M. J., Bejarano, E. R., Daga, R. R., & Jiménez, J. (1999) · Genetics · doi:10.1093/genetics/153.4.1561 · Cited by 43 · see citing works
Oxelmark, E., Knoblauch, R. E., Arnal, S. M., Su, L. F., Schapira, M., & Garabedian, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305960200 · Cited by 38 · see citing works
Intracellular dynamics of the Hsp90 co-chaperone p23 is dictated by Hsp90.
Picard, D. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.10.009 · Cited by 38 · see citing works
Properties of the co‐chaperone protein p23 erroneously attributed to ALG‐2 (apoptosis‐linked gene 2)
Mollerup, J., Krogh, T. N., Nielsen, P. F., & Berchtold, M. W. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01310-3 · Cited by 32 · see citing works
The co‐chaperone p23 is degraded by caspases and the proteasome during apoptosis
Mollerup, J., & Berchtold, M. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.06.045 · Cited by 25 · see citing works
Cox, M. B., & Miller, C. A. (2003) · Molecular Pharmacology · doi:10.1124/mol.64.6.1549 · Cited by 22 · see citing works
Contribution of N‐ and C‐terminal domains to the function of Hsp90 in Saccharomyces cerevisiae
Scheibel, T., Weikl, T., Rimerman, R. A., Smith, D. F., Lindquist, S. L., & Büchner, J. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01632.x · Cited by 16 · see citing works
Flagged first, then by citations
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Targeting the dynamic HSP90 complex in cancer
Trepel, J. B., Mollapour, M., Giaccone, G., & Neckers, L. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2887 · Cited by 1,523 · see citing works
Hsp90 Molecular Chaperone Inhibitors: Are We There Yet?
Neckers, L., & Workman, P. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1000 · Cited by 960 · see citing works
Verghese, J., Abrams, J., Wang, Y., & Morano, K. A. (2012) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.05018-11 · Cited by 575 · see citing works
The Hsp90 chaperone machinery: Conformational dynamics and regulation by co-chaperones
Li, J., Soroka, J., & Buchner, J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.09.003 · Cited by 498 · see citing works
Post-translational modifications of Hsp90 and their contributions to chaperone regulation
Mollapour, M., & Neckers, L. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.07.018 · Cited by 288 · see citing works
Asymmetric Activation of the Hsp90 Dimer by Its Cochaperone Aha1
Retzlaff, M., Hagn, F., Mitschke, L., Heßling, M., Gugel, F., Kessler, H., Richter, K., & Büchner, J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.006 · Cited by 244 · see citing works
Swe1Wee1-Dependent Tyrosine Phosphorylation of Hsp90 Regulates Distinct Facets of Chaperone Function
Mollapour, M., Tsutsumi, S., Donnelly, A. C., Beebe, K., Tokita, M. J., Lee, M.-J., Lee, S., Morra, G., Bourboulia, D., Scroggins, B. T., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.005 · Cited by 196 · see citing works
The role of Hsp90 in protein complex assembly
Makhnevych, T., & Houry, W. A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.09.001 · Cited by 184 · 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
The ‘active life’ of Hsp90 complexes
Prodromou, C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.07.020 · Cited by 171 · see citing works
Hsp90 is regulated by a switch point in the C‐terminal domain
Retzlaff, M., Stahl, M., Eberl, H. C., Lagleder, S., Beck, J., Kessler, H., & Büchner, J. (2009) · EMBO Reports · doi:10.1038/embor.2009.153 · Cited by 171 · see citing works
Heat Shock Protein 90 as a Drug Target against Protozoan Infections
Pallavi, R., Roy, N., Nageshan, R. K., Talukdar, P., Pavithra, S. R., Reddy, R., Sivaramakrishnan, V., Kumar, R., Gupta, A. K., Singh, R. K., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.155317 · Cited by 167 · see citing works
Mixed Hsp90–cochaperone complexes are important for the progression of the reaction cycle
Li, J., Richter, K., & Buchner, J. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1965 · Cited by 155 · 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
Neckers, L., Blagg, B. S. J., Haystead, T., Trepel, J. B., Whitesell, L. J., & Picard, D. (2018) · Cell Stress and Chaperones · doi:10.1007/s12192-018-0877-2 · Cited by 121 · see citing works
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He, Y., Peng, S., Wang, J., Chen, H., Cong, X., Chen, A., Hu, M., Qin, M., Wu, H., Gao, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms13122 · Cited by 105 · see citing works
Place, R. F., & Noonan, E. J. (2013) · Cell Stress and Chaperones · doi:10.1007/s12192-013-0456-5 · Cited by 85 · see citing works
Bhattacharya, K., & Picard, D. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03962-z · Cited by 73 · see citing works
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Wolmarans, A., Lee, B., Spyracopoulos, L., & LaPointe, P. (2016) · Scientific Reports · doi:10.1038/srep33179 · Cited by 72 · see citing works
Mini-review: Foldosome regulation of androgen receptor action in prostate cancer
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Miyata, Y., Koren, J., Kiray, J., Dickey, C. A., & Gestwicki, J. E. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.11.88 · Cited by 64 · see citing works
Simpson, N., Lambert, W. M., Watkins, R. A., Giashuddin, S., Huang, S., Oxelmark, E., Arju, R., Hochman, T., Goldberg, J. D., Schneider, R. J., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1590 · Cited by 11 · see citing works
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Hombach, A., Ommen, G., MacDonald, A., & Clos, J. (2014) · Journal of Cell Science · doi:10.1242/jcs.157297 · Cited by 60 · see citing works
Song, D., Li, L.-S., Heaton-Johnson, K. J., Arsenault, P. R., Master, S. R., & Lee, F. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.440552 · Cited by 58 · see citing works
Chatterjee, S., & Tatu, U. (2017) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0005836 · Cited by 57 · see citing works
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Mechanisms of Resistance to Hsp90 Inhibitor Drugs: A Complex Mosaic Emerges
Piper, P. W., & Millson, S. H. (2011) · Pharmaceuticals · doi:10.3390/ph4111400 · Cited by 53 · see citing works
Reebye, V., Querol Cano, L., Lavery, D. N., Brooke, G. N., Powell, S. M., Chotai, D., Walker, M. M., Whitaker, H. C., Wait, R., Hurst, H. C., et al. (2012) · Molecular Endocrinology · doi:10.1210/me.2012-1056 · Cited by 47 · see citing works
Discovery and Biological Activity of 6BrCaQ as an Inhibitor of the Hsp90 Protein Folding Machinery
Audisio, D., Messaoudi, S., Cegielkowski, L., Peyrat, J., Brion, J., Methy‐Gonnot, D., Radanyi, C., Renoir, J., & Alami, M. (2011) · ChemMedChem · doi:10.1002/cmdc.201000489 · Cited by 48 · see citing works
Dean, M. E., & Johnson, J. L. (2020) · Cell Stress and Chaperones · doi:10.1007/s12192-020-01167-0 · Cited by 48 · see citing works
Wider, D., Gulli, M., Briand, P.-A., Tatu, U. S., & Picard, D. (2009) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2008.12.011 · Cited by 45 · see citing works
Mutations that increase both Hsp90 ATPase activity in vitro and Hsp90 drug resistance in vivo.
Żurawska, A., Urbański, J., Matulienė, J., Baraniak, J., Klejman, M. P., Filipek, S., Matulis, D., & Bieganowski, P. (2010) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamcr.2010.03.002 · Cited by 39 · see citing works
Blacklock, K. M., & Verkhivker, G. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071936 · Cited by 38 · see citing works
Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery
Wang, L., Xu, X., Jiang, Z., & You, Q. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.01.018 · Cited by 37 · see citing works
The co‐chaperone p23 promotes prostate cancer motility and metastasis
Querol Cano, L., Lavery, D. N., Sin, S., Spanjaard, E., Brooke, G. N., Tilman, J. D., Abroaf, A., Gaughan, L., Robson, C. N., Heer, R., et al. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2014.08.014 · Cited by 33 · see citing works
“However, the yeast p23 homologue, Sba1, was shown to protect cells against the effects of HSP90 inhibitors such as geldanamycin or radicicol (Forafonov et al., 2008) and here we show that both androgen and antiandrogens can increase p23 protein levels.”
BackgroundA review of multi-domain and flexible molecular chaperones studies by small-angle X-ray scattering
Borges, J. C., Seraphim, T. V., Dores-Silva, P. R., & Barbosa, L. R. S. (2016) · Biophysical Reviews · doi:10.1007/s12551-016-0194-x · Cited by 32 · see citing works
Tosylcyclonovobiocic acids promote cleavage of the hsp90-associated cochaperone p23.
Radanyi, C., Bras, G. L., Bouclier, C., Messaoudi, S., Peyrat, J., Brion, J., Alami, M., & Renoir, J. (2009) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2008.12.102 · Cited by 28 · see citing works
Rehn, A., & Büchner, J. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-11731-7_6 · Cited by 30 · see citing works
Daneri-Becerra, C., Valeiras, B., Gallo, L. I., Lagadari, M., & Galigniana, M. D. (2020) · Journal of Cell Science · doi:10.1242/jcs.253401 · Cited by 28 · see citing works
Hsp90 inhibition: Elimination of shock and stress
Duerfeldt, A. S., & Blagg, B. S. J. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.06.108 · Cited by 28 · see citing works
The Interaction Networks of Hsp70 and Hsp90 in the Plasmodium and Leishmania Parasites
Seraphim, T. V., Ramos, C. H., & Borges, J. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1130-1_17 · Cited by 19 · see citing works
The C-terminal region of the human p23 chaperone modulates its structure and function
Seraphim, T. V., Gava, L. M., Mokry, D. Z., Cagliari, T. C., Barbosa, L. R. S., Ramos, C. H. I., & Borges, J. C. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.10.015 · Cited by 27 · see citing works
Hsp-90 and the biology of nematodes
Him, N. A., Gillan, V., Emes, R. D., Maitland, K., & Devaney, E. (2009) · BMC Evolutionary Biology · doi:10.1186/1471-2148-9-254 · Cited by 26 · see citing works
Liu, X., Zou, L.-M., Zhu, L., Zhang, H., Du, C.-H., Li, Z., Gao, C., Zhao, X.-X., Bao, S.-L., & Zheng, H.-Y. (2012) · Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis · doi:10.1016/j.leukres.2012.05.003 · Cited by 27 · see citing works
Millson, S. H., Prodromou, C., & Piper, P. W. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.01.031 · Cited by 25 · see citing works
Horvat, N. K., Armstrong, H., Lee, B. L., Mercier, R., Wolmarans, A., Knowles, J., Spyracopoulos, L., & LaPointe, P. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.04.002 · Cited by 24 · see citing works
No stress – Hsp90 and signal transduction inLeishmania
Hombach, A., & Clos, J. (2014) · Parasitology · doi:10.1017/s0031182013002151 · Cited by 24 · see citing works
Chua, C.-S., Low, H., Goo, K., & Sim, T. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0275-0 · Cited by 22 · see citing works
Batista, F. A. H., Almeida, G. S., Seraphim, T. V., Silva, K. P., Murta, S. M. F., Barbosa, L. R. S., & Borges, J. (2015) · The FEBS Journal · doi:10.1111/febs.13141 · Cited by 21 · see citing works
Bartsch, K., Hombach, A., & Clos, J. (2017) · Cell Stress and Chaperones · doi:10.1007/s12192-017-0800-2 · Cited by 19 · see citing works
Bharadwaj, S., Lee, K. E., Dwivedi, V., Yadava, U., & Kang, S.-G. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29229 · Cited by 18 · see citing works
Co-chaperones of Hsp90 in Plasmodium falciparum and their concerted roles in cellular regulation
Chua, C.-S., Low, H., & Sim, T. (2014) · Parasitology · doi:10.1017/s0031182013002084 · Cited by 17 · see citing works
Chua, C. S., Low, H., Lehming, N., & Sim, T. S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.10.021 · Cited by 18 · see citing works
Leishmania donovani P23 protects parasites against HSP90 inhibitor-mediated growth arrest
Hombach, A., Ommen, G., Sattler, V., & Clos, J. (2015) · Cell Stress and Chaperones · doi:10.1007/s12192-015-0595-y · Cited by 18 · see citing works
Johnson, J. L., Zuehlke, A. D., Tenge, V. R., & Langworthy, J. C. (2014) · Current Genetics · doi:10.1007/s00294-014-0432-3 · Cited by 17 · see citing works
Silva, N. S. M., Seraphim, T. V., Minari, K., Barbosa, L. R. S., & Borges, J. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.11.161 · Cited by 13 · see citing works
Echeverria, P. C., Forafonov, F., Pandey, D., Muhlebach, G., & Picard, D. (2011) · BioData Mining · doi:10.1186/1756-0381-4-15 · Cited by 15 · see citing works
Self-citationKröber-Boncardo, C., Lorenzen, S., Brinker, C., & Clos, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-72724-x · Cited by 12 · see citing works
Hsp90 Co-chaperones as Drug Targets in Cancer: Current Perspectives
Edkins, A. L. (2016) · Topics in medicinal chemistry · doi:10.1007/7355_2015_99 · Cited by 13 · see citing works
Ball, B., Sukumaran, A., Pladwig, S., Kazi, S., Chan, N., Honeywell, E., Modrakova, M., & Geddes‐McAlister, J. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.00152-24 · Cited by 14 · see citing works
p23 and Aha1: Distinct Functions Promote Client Maturation
Biebl, M. M., & Büchner, J. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-14740-1_6 · Cited by 9 · see citing works
Millson, S. H., Nuttall, J. M., Mollapour, M., & Piper, P. W. (2009) · Yeast · doi:10.1002/yea.1670 · Cited by 9 · see citing works
HOP expression is regulated by p53 and RAS and characteristic of a cancer gene signature
Mattison, S. A., Blatch, G. L., & Edkins, A. L. (2016) · Cell Stress and Chaperones · doi:10.1007/s12192-016-0755-8 · Cited by 9 · see citing works
Kolar, M., Dobčnik, D., & Radić, N. (2000) · PubMed · Cited by 9 · see citing works
Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity
Backe, S. J., Woodford, M. R., Ahanin, E. F., Sager, R., Bourboulia, D., & Mollapour, M. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-14740-1_11 · Cited by 8 · see citing works
Ko, Y., Chun, J., Yang, H., & Kim, D. (2023) · Molecular Plant Pathology · doi:10.1111/mpp.13308 · Cited by 5 · see citing works
Overview of Molecular Chaperones in Health and Disease
Wang, T., Echeverría, P. C., & Picard, D. (2013) · Royal Society of Chemistry eBooks · doi:10.1039/9781849739689-00001 · Cited by 5 · see citing works
Exploiting Cancer Dependence on Molecular Chaperones
Sharp, S. Y., Jones, K., & Workman, P. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-396521-9.00009-7 · Cited by 5 · see citing works
Sulfhydryl-Reactive Phytochemicals as Dual Activators of Transcription Factors NRF2 and HSF1
Dinkova‐Kostova, A. T., Zhang, Y., Naidu, S. D., Kostov, R. V., Pheely, A., & Calabrese, V. (2013) · Springer eBooks · doi:10.1007/978-3-319-00581-2_6 · Cited by 4 · see citing works
Hydrating for Resistance to Radicicol
Duerfeldt, A. S., & Blagg, B. S. J. (2009) · ACS Chemical Biology · doi:10.1021/cb9000712 · Cited by 4 · see citing works
Cruz, D. G. D. L., Castillo, D. A., Trujillo, C., Medina, C. A., Hurtado, V., Gil, J., Padmanabhan, M. S., Restrepo, S., Dinesh‐Kumar, S. P., Germain, H., et al. (2025) · Molecular Plant-Microbe Interactions · doi:10.1094/mpmi-08-24-0086-r · Cited by 3 · see citing works
Plesofsky, N. S. (2014) · ASM Press eBooks · doi:10.1128/9781555816636.ch32 · Cited by 3 · 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
Cyclophilin A is a mitochondrial factor that forms antiapoptotic complexes with p23Preprint
Daneri-Becerra, C., Valeiras, B., Lagadari, M., & Galigniana, M. D. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.21.261982 · Cited by 1 · see citing works
Exploiting the Dependency of Cancer Cells on Molecular Chaperones
Sharp, S. Y., Howes, J. E., & Workman, P. (2013) · Royal Society of Chemistry eBooks · doi:10.1039/9781849739689-00126
Simpson, N. E., Lambert, W. M., Watkins, R. A., Giashuddin, S. M., Huang, S.-T. J., Oxelmark, E., Arju, R., Hochman, T., Goldberg, J. D., Schneider, R. J., et al. (2023) · doi:10.1158/0008-5472.c.6500681
Simpson, N. E., Lambert, W. M., Watkins, R. A., Giashuddin, S. M., Huang, S.-T. J., Oxelmark, E., Arju, R., Hochman, T., Goldberg, J. D., Schneider, R. J., et al. (2023) · doi:10.1158/0008-5472.c.6500681.v1
Ball, B., Sukumaran, A., Pladwig, S., Kazi, S., Chan, N., Modrakova, M., & Geddes‐McAlister, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.03.535320
- Authors
- Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C., & Picard, D.
- Affiliations
- University of Geneva (CH)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Picard, Didier
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2008-05-01
- Volume
- 28
- Issue
- 10
- Pages
- 3446-3456
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2423160
- OpenAlex
- W2041894424
- Cited by
- 84
- References
- 64
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 13 · 2013: 9 · 2012: 6
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fondation Medic
- 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 › Fungal and yeast genetics research
- Keywords
- Hsp90 co-chaperone, Hsp90 inhibitors, chaperone activity, structure-function relationship, protein-protein interfaces, Saccharomyces cerevisiae, sequence divergence
- MeSH terms
- Prostaglandin-E Synthases, Amino Acid Sequence, Animals, Base Sequence, Cells, Cultured, DNA, Fungal, Genes, Fungal, Genetic Complementation Test, Models, Molecular, Phenotype, Protein Binding, Recombinant Proteins, Saccharomyces cerevisiae, Mutagenesis, Site-Directed, Point Mutation, Sequence Deletion, Sequence Homology, Amino Acid, DNA Primers, Molecular Chaperones, HSP90 Heat-Shock Proteins, Intramolecular Oxidoreductases, Saccharomyces cerevisiae Proteins, Mice
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