The Influence of ATP and p23 on the Conformation of hsp90
Open accessAbstract
The chaperoning activity of the heat shock protein hsp90 is directed, in part, by the binding and hydrolysis of ATP and also by association with co-chaperone proteins. One co-chaperone, p23, binds to hsp90 only when hsp90 is in a conformation induced by the binding of ATP. Once formed, the p23-hsp90 complex is very stable upon the removal of ATP and dissipates at 30 degrees with a half-life of about 45 min. This was shown to be due to the high stability of the ATP-induced state of hsp90, not to the rate of p23 dissociation. Further stabilization of this ATP-induced state is achieved by including molybdate or by use of the ATP analogue ATPgammaS. This conformational state of hsp90 is correlated with the tight binding of ADP resulting from hydrolysis of bound ATP. Both p23 and molybdate enhance and stabilize the nucleotide-bound state of hsp90, and this state is maximized by the presence of both agents. These results can be explained in a model where the binding of ATP induces a conformational transition in hsp90 that traps the nucleotide and is committed to ATP hydrolysis. p23 specifically recognizes this state and may also facilitate subsequent steps in the chaperoning cycle.
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p23 selectively binds to the ATP form of Hsp90, stabilizes the closed state, and promotes Hsp90 interactions with client proteins.
“Through selective binding to the ATP form of Hsp90, p23 stabilizes the 'closed' state and promotes Hsp90 interactions with client proteins (14, 33).”
From FKBP51 Promotes Assembly of the Hsp90 Chaperone Complex and Regulates Androgen Receptor Signaling in Prostate Cancer Cells (2010) · cites this paper as [33]
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Young, J. C., Moarefi, I., & Hartl, F. U. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200104079 · Cited by 826 · 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
In Vivo Function of Hsp90 Is Dependent on ATP Binding and ATP Hydrolysis
Obermann, W. M. J., Sondermann, H., Russo, A. A., Pavletich, N. P., & Hartl, F. U. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.4.901 · Cited by 593 · see citing works
Hsp90: Chaperoning signal transduction
Richter, K., & Büchner, J. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.1131 · Cited by 570 · see citing works
Grenert, J. P., Sullivan, W. P., Fadden, P., Haystead, T., Clark, J., Mimnaugh, E. G., Krutzsch, H. C., Ochel, H.-J., Schulte, T. W., Sausville, E. A., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23843 · Cited by 568 · see citing works
Self-citationFunctional requirement of p23 and Hsp90 in telomerase complexesPreprint
Holt, S. E., Aisner, D. L., Baur, J. A., Tesmer, V. M., Dy, M., Ouellette, M., Trager, J. B., Morin, G. B., Toft, D. O., Shay, J. W., et al. (1999) · Genes & Development · doi:10.1101/gad.13.7.817 · Cited by 533 · see citing works
Self-citationMarcu, M. G., Chadli, A., Bouhouche, I., CATELLI, M. G., & Neckers, L. Μ. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003701200 · Cited by 504 · 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
Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)‐domain co‐chaperones
Prodromou, C., Siligardi, G., O’Brien, R., Woolfson, D. N., Regan, L., Panaretou, B., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1999) · The EMBO Journal · doi:10.1093/emboj/18.3.754 · Cited by 422 · see citing works
Disassembly 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
Chaperone 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 · see citing works
Self-citationStructure and in vivo function of Hsp90
Pearl, L. H., & Prodromou, C. (2000) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(99)00047-0 · Cited by 317 · see citing works
Hu, J., Toft, D. O., & Seeger, C. (1997) · The EMBO Journal · doi:10.1093/emboj/16.1.59 · Cited by 312 · see citing works
Self-citationFolding of the Glucocorticoid Receptor by the Heat Shock Protein (hsp) 90-based Chaperone Machinery
Dittmar, K. D., Demady, D. R., Stancato, L. F., Krishna, P., & Pratt, W. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.21213 · Cited by 265 · see citing works
The Assembly of Progesterone Receptor-hsp90 Complexes Using Purified Proteins
Kosano, H., Stensgard, B. A., Charlesworth, M. C., McMahon, N., & Toft, D. O. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.32973 · Cited by 239 · see citing works
Self-citationMcLaughlin, S. H., Smith, H. W., & Jackson, S. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5245 · Cited by 239 · see citing works
Nucleotides and Two Functional States of hsp90
Sullivan, W., Stensgard, B. A., Caucutt, G., Bartha, B. B., McMahon, N., Alnemri, E. S., Litwack, G., & Toft, D. O. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.8007 · Cited by 235 · see citing works
Self-citationBinding 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
Self-citationPolypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the co‐chaperone p23
Young, J. C., & Hartl, F. U. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5930 · Cited by 230 · see citing works
Grenert, J. P., Johnson, B. D., & Toft, D. O. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.25.17525 · Cited by 223 · see citing works
Self-citationCharacterization of a novel 23-kilodalton protein of unactive progesterone receptor complexes
Johnson, J. L., Beito, T., Krco, C., & Toft, D. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1956-1963.1994 · Cited by 204 · see citing works
Self-citationInhibition of progesterone receptor activation by sodium molybdate.
Nishigori, H., & Toft, D. (1980) · Biochemistry · doi:10.1021/bi00542a012 · Cited by 204 · see citing works
Self-citationFreeman, 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
Self-citationChadli, A., Bouhouche, I., Sullivan, W. J., Stensgard, B., McMahon, N., Catelli, M., & Toft, D. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.220430297 · Cited by 159 · see citing works
Self-citationHSP40 Binding Is the First Step in the HSP90 Chaperoning Pathway for the Progesterone Receptor
Hernández, M. P., Chadli, A., & Toft, D. O. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111445200 · Cited by 144 · see citing works
Self-citationBinding of ATP to Heat Shock Protein 90
Garnier, C., Lafitte, D., Tsvetkov, P. O., Barbier, P., Leclerc, J., Millot, J., Briand, C. M., Makarov, A. А., CATELLI, M. G., & Peyrot, V. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111874200 · Cited by 142 · 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
Self-citationWeikl, T., Muschler, P., Richter, K., Veit, T., Reinstein, J., & Büchner, J. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4157 · Cited by 118 · see citing works
Weikl, T., Abelmann, K., & Buchner, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3172 · Cited by 97 · see citing works
Continuous recycling: a mechanism for modulatory signal transduction.
Freeman, B. C., & Yamamoto, K. R. (2001) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/s0968-0004(01)01834-5 · Cited by 81 · see citing works
Hartson, S., Thulasiraman, V., Huang, W., Whitesell, L., & Matts, R. (1999) · Biochemistry · doi:10.1021/bi983027s · Cited by 77 · see citing works
Regulation of Heat Shock Protein 90 ATPase Activity by Sequences in the Carboxyl Terminus*
Owen, B., Sullivan, W., Felts, S., & Toft, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111450200 · Cited by 69 · see citing works
Self-citationPrapapanich, V., Chen, S.-Y., & Smith, D. F. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.944 · Cited by 54
Morishima, Y., Kanelakis, K. C., Murphy, P. J. M., Shewach, D. S., & Pratt, W. (2001) · Biochemistry · doi:10.1021/bi002399+ · Cited by 41 · see citing works
Aluminum fluoride inhibition of glucocorticoid receptor inactivation and transformation.
Housley, P. R. (1990) · Biochemistry · doi:10.1021/bi00466a022 · Cited by 11
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- Chadli, A., Bouhouche, I., Sullivan, W., Stensgard, B., McMahon, N., Catelli, M. G., and Toft, D. O. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 12524 -12529
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The Aryl Hydrocarbon Receptor Complex and the Control of Gene Expression
Beischlag, T. V., Morales, J. L., Hollingshead, B. D., & Perdew, G. H. (2008) · Critical Reviews™ in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v18.i3.20 · Cited by 727 · see citing works
“, p23-bound) conformation of HSP90 complexes.(160) Additionally, the increased formation of AhR-ARNT DNA-bound complexes in the presence of p23 has been reported, as determined by mobility gel shift assay.”
BackgroundHsp70 and Hsp90—a relay team for protein folding
Wegele, H., Müller, L., & Büchner, J. (2004) · Springer eBooks · doi:10.1007/s10254-003-0021-1 · Cited by 603 · 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
Role of molecular chaperones in steroid receptor action.
Pratt, W., Galigniana, M., Morishima, Y., & Murphy, P. J. M. (2004) · Essays in Biochemistry · doi:10.1042/bse0400041 · Cited by 259 · see citing works
“This is the conformation of hsp90 that recognizes p23, which now binds the receptor-bound hsp90 and stabilizes the GR–hsp90 heterocomplex [15].”
BackgroundAsymmetric 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
“One of the inhibitors, p23/Sba1, binds preferentially to the N terminally closed, nucleotide-bound state (Ali et al., 2006; McLaughlin et al., 2006; Richter et al., 2004; Sullivan et al., 2002), whereas the cochaperone Hop/Sti1 binds to the open conformation of Hsp90, the putative resting state (Onuoha et al.”
BackgroundStructural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery
Meyer, P., Prodromou, C., Liao, C., Hu, B., Roe, S., Vaughan, C., Vlašić, I., Panaretou, B., Piper, P., & Pearl, L. H. (2004) · EMBO Journal · doi:10.1038/sj.emboj.7600141 · Cited by 244 · see citing works
“…co-chaperone p23/Sba1, which only associates with Hsp90 in the ATP-bound and N-terminally dimerised form (Chadli et al, 2000; Prodromou et al, 2000; Sullivan et al, 2002), slows down the cycle by stabilising the closed conformation of the clamp, but as it binds after ATP, it cannot completely…”
BackgroundJensen, M., Schoepfer, J., Radimerski, T., Massey, A., Guy, C. T., Brueggen, J., Quadt, C., Buckler, A., Cozens, R., Drysdale, M., et al. (2008) · Breast Cancer Research · doi:10.1186/bcr1996 · Cited by 237 · see citing works
“An alternative method of studying the cellular effects of HSP90 inhibitors, which more closely monitors the catalytic cycle of HSP90, is through the evaluation of disruption of the HSP90p23 complex [ 28 ].”
MethodThe 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 · see citing works
Characterization of Celastrol to Inhibit Hsp90 and Cdc37 Interaction*
Zhang, T., Li, Y.-Y., Yu, Y.-K., Zou, P., Jiang, Y.-Q., & Sun, D.-X. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.051532 · Cited by 189 · see citing works
Murphy, P. J. M., Morishima, Y., Kovacs, J. J., Yao, T.-P., & Pratt, W. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506997200 · Cited by 167 · 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 · see citing works
Ni, L., Yang, C.-S., Gioeli, D., Frierson, H., Toft, D. O., & Paschal, B. M. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01891-08 · Cited by 155 · see citing works
Self-citationShimamura, T., Perera, S. A., Foley, K. P., Sang, J., Rodig, S. J., Inoue, T., Chen, L., Li, D., Carretero, J., Li, Y.-C., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2967 · Cited by 165 · see citing works
“HSP90 binds to co-chaperones, including p23, in an ATP-dependent manner and this assembly of the catalytically active complex is a prerequisite for efficient chaperone function (38).”
Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery
Meyer, P., Prodromou, C., Liao, C., Hu, B., Roe, S., Vaughan, C., Vlašić, I., Panaretou, B., Piper, P., & Pearl, L. H. (2004) · EMBO Journal · doi:10.1038/sj.emboj.7600060 · Cited by 153 · see citing works
“…co-chaperone p23/Sba1, which only associates with Hsp90 in the ATP-bound and N-terminally dimerised form (Chadli et al, 2000; Prodromou et al, 2000; Sullivan et al, 2002), slows down the cycle by stabilising the closed conformation of the clamp, but as it binds after ATP, it cannot completely…”
BackgroundHuman Sgt1 Binds HSP90 through the CHORD-Sgt1 Domain and Not the Tetratricopeptide Repeat Domain*
Lee, Y.-T., Jacob, J., Michowski, W., Nowotny, M., Kuźnicki, J., & Chazin, W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400215200 · Cited by 136 · see citing works
Harst, A., Lin, H.-Y., & Obermann, W. (2005) · Biochemical Journal · doi:10.1042/bj20041283 · Cited by 121 · 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
Self-citationTargeting Hsp90 and its co-chaperones to treat Alzheimer’s disease
Blair, L. J., Sabbagh, J. J., & Dickey, C. (2014) · Expert opinion on therapeutic targets · doi:10.1517/14728222.2014.943185 · Cited by 113 · see citing works
“5 Hsp90/p23 p23 is a co-chaperone that binds exclusively to ATP-bound Hsp90, but can remain bound even following ATP hydrolysis [90].”
BackgroundMultiple 40-kDa heat-shock protein chaperones function in Tom70-dependent mitochondrial import.
Bhangoo, M. K., Tzankov, S., Fan, A., Dejgaard, K., Thomas, D. Y., & Young, J. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-01-0088 · Cited by 98 · see citing works
“Cochaperones that do not belong to these structural families include Cdc37, p23, and Aha1. p23 stabilizes the ATP- and substrate-binding state of Hsp90, whereas the recently discovered Aha1 stimulates the Hsp90 ATPase (Panaretou et al., 2002; Sullivan et al., 2002; Lotz et al., 2003; Morishima et al., 2003; Pearl and…”
BackgroundInfluentialCooperation of heat shock protein 90 and p23 in aryl hydrocarbon receptor signaling
Cox, M. B., & Miller, C. A. (2004) · Cell Stress and Chaperones · doi:10.1379/1466-1268(2004)009 · Cited by 86 · see citing works
Gano, J., & Simon, J. A. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900261-mcp200 · Cited by 85 · see citing works
Quintá, H., Maschi, D., Gomez-Sanchez, C., Piwien-Pilipuk, G., & Galigniana, M. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06970.x · Cited by 86 · see citing works
p23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity
Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C., & Picard, D. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.02246-07 · Cited by 84 · 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).”
BackgroundRegulation of cytosolic prostaglandin E synthase by phosphorylation.
Kobayashi, T., Nakatani, Y., Tanioka, T., Tsujimoto, M., Nakajo, S., Nakaya, K., Murakami, M., & Kudo, I. (2004) · Biochemical Journal · doi:10.1042/bj20040118 · Cited by 84 · see citing works
P-Glycoprotein–Mediated Resistance to Hsp90-Directed Therapy Is Eclipsed by the Heat Shock Response
McCollum, A. K., TenEyck, C. J., Stensgard, B. A., Morlan, B. W., Ballman, K. V., Jenkins, R. B., Toft, D. O., & Erlichman, C. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5175 · Cited by 76 · see citing works
“Hsp90 activity was monitored by examining its binding to p23, a cochaperone that binds Hsp90 only in the presence of ATP ( 40 ).”
Self-citationRegulatory role of the 90-kDa-heat-shock protein (Hsp90) and associated factors on gene expression
Erlejman, A. G., Lagadari, M., Toneatto, J., Piwien‐Pilipuk, G., & Galigniana, M. D. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2013.12.006 · Cited by 74 · see citing works
“lized by p23 binding, and other TPR proteins such as the highmolecular weight immunophilins are efficiently recruited [53,54].”
BackgroundDefining the Requirements for Hsp40 and Hsp70 in the Hsp90 Chaperone Pathway*
Cintron, N. S., & Toft, D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605417200 · Cited by 77 · see citing works
Self-citationLee, K., Thwin, A. C., Nadel, C. M., Tse, E., Gates, S. N., Gestwicki, J. E., & Southworth, D. R. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.023 · Cited by 76 · see citing works
Intrinsic Inhibition of the Hsp90 ATPase Activity
Richter, K., Moser, S. C., Hagn, F., Friedrich, R., Hainzl, O., Heller, M., Schlee, S., Kessler, H., Reinstein, J., & Büchner, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510142200 · Cited by 75 · see citing works
In Vitro Epsilon RNA-Dependent Protein Priming Activity of Human Hepatitis B Virus Polymerase
Jones, S. A., Boregowda, R. K., Spratt, T. E., & Hu, J.-M. (2012) · Journal of Virology · doi:10.1128/jvi.07137-11 · Cited by 69 · see citing works
“639301; 1:500), and p23 (jj3; 1:2,000) (61).”
Lee, K., Thwin, A., Nadel, C., Tse, E., Gates, S., Gestwicki, J., & Southworth, D. (2021) · bioRxiv · doi:10.1101/2021.01.21.427690 · Cited by 65 · see citing works
“…the closed Hsp90 conformation Immunophilins are present with p23 in Hsp90-steroid hormone receptor maturation complexes (Ebong et al., 2016; Johnson and Toft, 1994; Nair et al., 1997), indicating potential binding to the closed, ATP conformation of Hsp90 (Ali et al., 2006; Sullivan et al., 2002).”
Tau Protein Squired by Molecular Chaperones During Alzheimer’s Disease
Gorantla, N. V., & Chinnathambi, S. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1174-3 · Cited by 112 · see citing works
Localization of Sites of Interaction between p23 and Hsp90 in Solution
Martinez‐Yamout, M. A., Venkitakrishnan, R. P., Preece, N. E., Kroon, G. J. A., Wright, P. E., & Dyson, H. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601759200 · Cited by 66 · see citing works
Biebl, M. M., Lopez, A., Rehn, A., Freiburger, L., Lawatscheck, J., Blank, B., Sattler, M., & Buchner, J. (2021) · Nature Communications · doi:10.1038/s41467-021-21063-0 · Cited by 58 · see citing works
Contributions of Co-Chaperones and Post-Translational Modifications Towards Hsp90 Drug Sensitivity
Walton‐Diaz, A., Khan, S., Bourboulia, D., Trepel, J. B., Neckers, L., & Mollapour, M. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.88 · Cited by 59 · see citing works
Molecular Pathways: Targeting Hsp90—Who Benefits and Who Does Not
Scaltriti, M., Dawood, S. S., & Cortés, J. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2138 · Cited by 67 · see citing works
“ATP binds to Hsp90 dimers, forcing them to assume a “closed” conformation, which in turn facilitates the interaction with the co-chaperone p23, and the dissociation from Hop (22-25).”
ZMYND10 functions in a chaperone relay during axonemal dynein assembly
Mali, G., Yeyati, P., Mizuno, S., Dodd, D. O., Tennant, P. A., Keighren, M., Lage, P. Z., Shoemark, A., García-Muñoz, A., Shimada, A., et al. (2017) · bioRxiv · doi:10.1101/233718 · Cited by 55
“For detecting HSP90 interactions, we included 807 sodium molybdate (Sigma-Aldrich) in the IP buffer aiming to reduce ATP hydrolysis and client 808 release(Sullivan et al., 2002).”
MethodXu, W.-P., Beebe, K., Chavez, J. D., Boysen, M., Lu, Y., Zuehlke, A., Keramisanou, D., Trepel, J., Prodromou, C., Mayer, M. P., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10463-y · Cited by 54 · see citing works
Involvement of molecular chaperone in protein-misfolding brain diseases.
Wankhede, N., Kale, M. B., Upaganlawar, A., Taksande, B., Umekar, M., Behl, T., Abdellatif, A., Bhaskaran, P. M., Dachani, S. R., Sehgal, A., et al. (2022) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2022.112647 · Cited by 53 · see citing works
Association between Hsp90 and the ClC-2 chloride channel upregulates channel function.
Hinzpeter, A., Lipecka, J., Brouillard, F., Baudoin-Legros, M., Dadlez, M., Edelman, A., & Fritsch, J. (2006) · American Journal of Physiology - Cell Physiology · doi:10.1152/ajpcell.00209.2005 · Cited by 51 · see citing works
“Lysis buffer was complemented with 10 mM sodium molybdate because it has been demonstrated to stabilize Hsp90/client protein complexes (60).”
MethodThe Assembly and Intermolecular Properties of the Hsp70-Tomm34-Hsp90 Molecular Chaperone Complex*
Trčka, F., Durech, M., Man, P., Hernychová, L., Muller, P., & Vojtěšek, B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.526046 · Cited by 50 · see citing works
“Conversely, molybdate stabilizes the nucleotide-bound “closed conformation” of Hsp90 (32).”
BackgroundTumor-Intrinsic and Tumor-Extrinsic Factors Impacting Hsp90-Targeted Therapy
Alarcon, S., Mollapour, M., Lee, M.-J., Tsutsumi, S., Lee, S., Kim, Y., Prince, T., Apolo, A., Giaccone, G., Xu, W.-P., et al. (2012) · Current molecular medicine · doi:10.2174/156652412803306729 · Cited by 47 · see citing works
“In contrast, the co-chaperones Hsp70-Hsp90 organizing protein (Hop) also known as STIP1 or STI1 (stress inducible protein 1), and cell division cycle 37 homolog (Cdc37) exert opposing activity to Aha1 by preventing the initial structural changes required for N-terminal dimerization, while the co-chaperone prostaglandi…”
BackgroundOxelmark, 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
Puente, L., Borris, D. J., Carrière, J., Kelly, J., & Megeney, L. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500166-mcp200 · Cited by 42 · see citing works
“One function of p23 is regulation of HSP90/HSPCB (38), which was also detected as an ESC-enriched putatively phosphorylated protein (Tables I and II).”
BackgroundHsp90 can accommodate the simultaneous binding of the FKBP52 and HOP proteins
Hildenbrand, Z. L., Molugu, S. K., Herrera, N., Ramirez, C., Xiao, C., & Bernal, R. A. (2011) · Oncotarget · doi:10.18632/oncotarget.225 · Cited by 38 · see citing works
A methylated lysine is a switch point for conformational communication in the chaperone Hsp90
Rehn, A., Lawatscheck, J., Jokisch, M.-L., Mader, S. L., Luo, Q., Tippel, F., Blank, B., Richter, K., Lang, K., Kaila, V. R. I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15048-8 · Cited by 38 · see citing works
Intracellular dynamics of the Hsp90 co-chaperone p23 is dictated by Hsp90
Picard, D. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.10.009 · Cited by 39 · see citing works
Echeverría, P. C., Briand, P.-A., & Picard, D. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.01099-15 · Cited by 39 · see citing works
“This 63 small acidic protein binds and stabilizes the ATP-bound state of Hsp90 (19-23).”
BackgroundA novel role for DYX1C1, a chaperone protein for both Hsp70 and Hsp90, in breast cancer
Chen, Y., Zhao, M.-Z., Wang, S., Chen, J., Wang, Y., Cao, Q.-H., Zhou, W., Liu, J., Xu, Z., Tong, G., et al. (2009) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-009-0568-6 · Cited by 32 · see citing works
“P23, the smallest protein in Hsp90 co-chaperone complexes, serves as an important modulator of Hsp90 (Johnson et al. 1994; Johnson and Toft 1994) and stabilizes its ATP-bound form to facilitate the formation of Hsp90 chaperone complexes ( Sullivan et al. 2002 ).”
BackgroundGeneral Structural and Functional Features of Molecular Chaperones.
Edkins, A., & Boshoff, A. (2021) · Advances in Experimental Medicine and Biology · doi:10.1007/978-94-007-7438-4_2 · Cited by 32 · see citing works
Picard, D., Suslova, E., & Briand, P.-A. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.08.026 · Cited by 32 · see citing works
In Vitro Epsilon RNA-Dependent Protein Priming Activity of Human Hepatitis B Virus Polymerase
Jones, S. A., Boregowda, R. K., Spratt, T. E., & Hu, J.-M. (2012) · Journal of Virology · doi:10.1128/jvi.02559-13 · Cited by 28
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. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.12.102 · Cited by 31 · 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
“[1] Sullivan WP, Owen BA, Toft DO.”
BackgroundHSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation
Chakraborty, A., Boel, N. M.-E., & Edkins, A. L. (2020) · Cells · doi:10.3390/cells9020272 · Cited by 29 · see citing works
“Sodium molybdate, in contrast, retains HSP90 in an ATP bound state [83], which has been shown to promote complex formation and stabilize other client interactions [84,85].”
BackgroundThe Hsp90 Co-chaperones Sti1, Aha1, and P23 Regulate Adaptive Responses to Antifungal Azoles
Gu, X., Xue, W., Yin, Y.-J., Liu, H.-W., Li, S.-J., & Sun, X.-Y. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01571 · Cited by 26 · 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
A Truncated Form of p23 Down-regulates Telomerase Activity via Disruption of Hsp90 Function*
Woo, S., An, S., Lee, H.-C., Jin, H.-O., Seo, S.-K., Yoo, D.-H., Lee, K.-H., Rhee, C., Choi, E.-J., Hong, S.-I., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.052720 · Cited by 25 · 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
“bound form of hsp90, and it facilitates subsequent steps in the chaperoning cycle [8].”
BackgroundGlucocorticoid receptor complexes form cooperatively with the Hsp90 co-chaperones Pp5 and FKBPs
Kaziales, A., Barkovits, K., Marcus, K., & Richter, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-67645-8 · Cited by 24 · see citing works
Park, S., Park, J.-A., Jeon, J.-H., & Lee, Y. (2019) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2019.051 · Cited by 24 · see citing works
“…of b-Rafmutated human melanoma tumor in vivo (Eccles et al., 2008). p23 is a co-chaperone of HSP90 and plays an important role in the activity of HSP90 and stabilization of client proteins by association with HSP90, and HSP90-p23 interaction requires ATP binding in HSP90 (Sullivan et al., 2002).”
BackgroundLee, C.-H., Park, J., Choi, J.-H., Yoo, K., Ryu, P., & Won, M. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.05.002 · Cited by 24 · see citing works
“The interaction between HSP90 and p23 requires ATP and occurs in the late stage of chaperone cycle (Sullivan et al., 2002).”
BackgroundInfluentialChua, 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
Chen, S., Wu, Y.-R., Gao, Y., Wu, C., Wang, Y.-T., Hou, C., Ren, M., Zhang, S.-Y., Zhu, Q., Zhang, J.-L., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113246 · Cited by 21 · see citing works
Xue, N., Jin, J., Liu, D., Yan, R., Zhang, S., Yu, X.-M., & Chen, X.-G. (2014) · Current Cancer Drug Targets · doi:10.2174/1568009614666140908101523 · Cited by 19 · see citing works
Durech, M., Trčka, F., Man, P., Blackburn, E., Hernychová, L., Dvořáková, P., Coufalová, D., Kavan, D., Vojtěšek, B., & Muller, P. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m116.058131 · Cited by 18 · see citing works
Characterization of orchardgrass p23, a flowering plant Hsp90 cohort protein
Cha, J., Ermawati, N., Jung, M. H., Su’udi, M., Kim, K.-Y., Kim, J., Han, C., Lee, K. H., & Son, D. (2008) · Cell Stress and Chaperones · doi:10.1007/s12192-008-0077-6 · Cited by 16 · see citing works
“After binding to Hsp90, p23 stabilizes the conformational state of Hsp90 by inhibition of ATP hydrolysis (McLaughlin et al. 2006).”
BackgroundInfluentialCo-chaperones of Hsp90 inPlasmodium falciparumand their concerted roles in cellular regulation
Chua, C., Low, H., & Sim, T. (2014) · Parasitology · doi:10.1017/s0031182013002084 · Cited by 18 · see citing works
Gaur, D., Singh, P. R., Guleria, J., Gupta, A., Kaur, S., & Sharma, D. (2020) · Genetics · doi:10.1534/genetics.120.303190 · Cited by 16 · see citing works
Nandi, S. K., Chakraborty, A., Panda, A. K., Ray, S. S., Kar, R., Bhunia, A., & Biswas, D. A. (2015) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0003661 · Cited by 15
“The interaction between HSPs and ATP is often reversible in nature [18, 45].”
BackgroundEcheverría, P. C., Forafonov, F., Pandey, D. P., Mühlebach, G., & Picard, D. (2011) · BioData Mining · doi:10.1186/1756-0381-4-15 · Cited by 16 · see citing works
“This ubiquitous acidic protein binds and stabilizes the ATP-bound dimeric form of Hsp90 [10,13,14], inhibits ATP hydrolysis and thereby traps Hsp90 in a state with high affinity for client proteins [15,16].”
BackgroundLe, M., Nakano, Y., Uyghurturk, D. A., Zhu, L., & DenBesten, P. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00925 · Cited by 14 · see citing works
“When HSP90 reaches a fully closed state, ATP hydrolysis occurs to release ADP and inorganic phosphate, and returns again to the open conformation (Sullivan et al., 2002; Colombo et al., 2008; Zhang et al., 2015).”
BackgroundIdentification and characterisation of a novel heat shock protein 90 inhibitor ONO4140
Eachkoti, R., Reddy, M. R. R., Lieu, Y., Cosenza, S., & Reddy, E. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.04.017 · Cited by 14 · see citing works
“The hsp90 inhibition property of ONO4140 was further validated by studying its cellular effects on the catalytic activity of HSP90 which can be monitored through the evaluation of disruption of the HSP90-p23 complex [35].”
BackgroundMethodSilva, 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
Madon-Simon, M., Grad, I., Bayo, P., Pérez, P., & Picard, D. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180035 · Cited by 10 · see citing works
Alao, J. P., Obaseki, I., Amankwah, Y. S., Nguyen, Q., Sugoor, M., Unruh, E., Popoola, H. O., Tehver, R., & Kravats, A. N. (2023) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.3c00260 · Cited by 9 · see citing works
Detecting HSP90 Phosphorylation
Mollapour, M., & Neckers, L. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-295-3_5 · Cited by 9 · see citing works
Small molecules targeting molecular chaperones for tau regulation: Achievements and challenges
He, C., Gu, J., Wang, D., Wang, K., Wang, Y., You, Q., & Wang, L. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115859 · Cited by 12 · 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
Dernovšek, J., Gradišek, N., Zajec, Ž., Urbančič, D., Cingl, J., Goričan, T., Grdadolnik, S., & Tomašič, T. (2024) · RSC Advances · doi:10.1039/d4ra05878j · Cited by 5 · see citing works
“To further investigate the e ff ect of substituents at this position, piperidine, morpholine, 4-hydroxypiperidine, and 4-aminopiperidine were attached to 10d and 10g to prepare analogs 14 – 16 , 18 – 21 and 23 – 24 .”
MethodCdc37 and protein kinase folding
Matts, R. L., & Caplan, A. J. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6401-2_16 · Cited by 4 · see citing works
“Molybdate, which is postulated to act as a mimic of the -phosphate of ATP, also inhibits Hsp90 function (Hartson et al., 1999; Johnson and Toft, 1995; Sullivan et al., 2002).”
BackgroundShi, Y.-F., Li, J., Zhong, Q., Chen, H., Ma, X.-Y., Hu, Y., Wang, Y.-S., Jiang, D., Zhou, X., Li, X., et al. (2025) · Journal of Pathology · doi:10.1002/path.6436 · Cited by 3 · see citing works
“However, as a molecular chaperone protein, HSP90 itself can also regulate the structure and activity of substrate proteins and may be regulated by other upstream signaling molecules or epigenetic modi fi cation enzyme, such as p23 [63], Aha1 [64], SIRT1 [65].”
Wang, M., Yang, J., Wang, D., Zhou, J., Qin, S.-B., Jiao, Y., & Wang, L. (2025) · Radiation Oncology · doi:10.1186/s13014-025-02661-4 · Cited by 3
“HSP27, HSP90, HSP70, and small molecule HSPs in the HSP family have anti-inflammatory effects in various ways [24, 25].”
Cha, J., Baek, D., Lee, K.-W., Cheong, M., Hong, S., & Son, D. (2018) · Acta Physiologiae Plantarum · doi:10.1007/s11738-018-2708-6 · Cited by 3
Intrinsically Disordered Chaperones and Neurodegeneration
Uversky, V. (2011) · doi:10.1002/9781118063903.ch1 · Cited by 3 · see citing works
Matlhodi, T., Makatsela, L. P., Gumede, N., & Mokoena, F. (2025) · Transactions of the Royal Society of South Africa. Royal Society of South Africa · doi:10.1080/0035919x.2025.2461304 · Cited by 2 · see citing works
Interplay between Hsp90 and TPR domain-containing proteins in steroidogenic signaling
Hildenbrand, Z., & Bernal, R. (2012) · Cell Cycle · doi:10.4161/cc.19889 · Cited by 2 · see citing works
Molekulare Effekte der Immunmodulation mit einem anti-CD4-Antikörper
Kieselbach, B. (2004) · doi:10.18452/15074 · Cited by 2
“Kinasen) von Hsp90 erforderlich ist (168), könnten eine gute Erklärung für die Notwendigkeit der p23 Regulation sein.”
BackgroundEmergence 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
Fiotaki, C., Goldfarb, D., & Giannouli, A. (2026) · Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6c03220
Buchner, J., & Walter, S. (2008) · Protein Science Encyclopedia · doi:10.1002/9783527610754.sf15
Chaperone Association with Telomere Binding Proteins
Depcrynski, A. (2009) · doi:10.25772/xxqt-1q10
- Authors
- Sullivan, W. P., Owen, B. A. L., & Toft, D. O.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Toft, David O.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 277
- Issue
- 48
- Pages
- 45942-45948
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2016643143
- Cited by
- 111
- References
- 39
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 8 · 2013: 3 · 2012: 6
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK059284, R01DK046249, DK 46249, DK 59284)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- HSP90, p23, ATP binding, protein conformation, co-chaperones, ATP hydrolysis, ADP binding, molybdate, ATP gamma S, chaperone cycle, conformational change
- MeSH terms
- Prostaglandin-E Synthases, Adenosine Triphosphate, Animals, Chickens, Humans, Phosphoproteins, Protein Binding, Protein Conformation, Molecular Chaperones, HSP90 Heat-Shock Proteins
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