HDAC6 Regulates Hsp90 Acetylation and Chaperone-Dependent Activation of Glucocorticoid Receptor
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The molecular chaperone heat shock protein 90 (Hsp90) and its accessory cochaperones function by facilitating the structural maturation and complex assembly of client proteins, including steroid hormone receptors and selected kinases. By promoting the activity and stability of these signaling proteins, Hsp90 has emerged as a critical modulator in cell signaling. Here, we present evidence that Hsp90 chaperone activity is regulated by reversible acetylation and controlled by the deacetylase HDAC6. We show that HDAC6 functions as an Hsp90 deacetylase. Inactivation of HDAC6 leads to Hsp90 hyperacetylation, its dissociation from an essential cochaperone, p23, and a loss of chaperone activity. In HDAC6-deficient cells, Hsp90-dependent maturation of the glucocorticoid receptor (GR) is compromised, resulting in GR defective in ligand binding, nuclear translocation, and transcriptional activation. Our results identify Hsp90 as a target of HDAC6 and suggest reversible acetylation as a unique mechanism that regulates Hsp90 chaperone complex activity.
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TSA induces acetylation of Hsp90 in eukaryotes.
“To further investigate the potential of acetylation to inhibit Hsp90 function, we used trichostatin A (TSA), which was shown to induce acetylation of Hsp90 in eukaryotes (17–20).”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [18]
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HDAC6 is a microtubule-associated deacetylase
Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.-F., & Yao, T.-P. (2002) · Nature · doi:10.1038/417455a · Cited by 2,403 · see citing works
Self-citationPratt, W., & Toft, D. (2003) · Experimental biology and medicine · doi:10.1177/153537020322800201 · Cited by 1,539 · see citing works
Self-citationKawaguchi, Y., Kovacs, J. J., McLaurin, A. C., Vance, J. M., Ito, A., & Yao, T. (2003) · Cell · doi:10.1016/s0092-8674(03)00939-5 · Cited by 1,529 · see citing works
Self-citationA 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
Haggarty, S. J., Koeller, K. M., Wong, J. C., Grozinger, C. M., & Schreiber, S. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0430973100 · Cited by 1,066 · see citing works
Functional domains of the human glucocorticoid receptor
Giguère, V., Hollenberg, S. M., Rosenfeld, M. G., & Evans, R. M. (1986) · Cell · doi:10.1016/0092-8674(86)90339-9 · Cited by 918 · see citing works
HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo
Zhang, Y., Li, N., Caron, C., Matthias, G., Hess, D., Khochbin, S., & Matthias, P. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg115 · Cited by 740 · see citing works
In vivo destabilization of dynamic microtubules by HDAC6‐mediated deacetylation
Matsuyama, A., Shimazu, T., Sumida, Y., Saito, A., Yoshimatsu, Y., Seigneurin‐Berny, D., Osada, H., Komatsu, Y., Nishino, N., Khochbin, S., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf682 · Cited by 720 · see citing works
Self-citationHsp90 inhibitors as novel cancer chemotherapeutic agents
Neckers, L. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02316-x · Cited by 677 · 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
Furumai, R., Komatsu, Y., Nishino, N., Khochbin, S., Yoshida, M., & Horinouchi, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.87 · Cited by 412 · see citing works
Self-citationPharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90
Schneider, C. B., Sepp‐Lorenzino, L., Nimmesgern, E., Ouerfelli, O., Danishefsky, S. J., Rosen, N. X., & Hartl, F. U. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14536 · Cited by 405 · see citing works
Modulation of p53, ErbB1, ErbB2, and Raf-1 Expression in Lung Cancer Cells by Depsipeptide FR901228
Yu, X. (2002) · CancerSpectrum Knowledge Environment · doi:10.1093/jnci/94.7.504 · Cited by 360 · see citing works
Xu, W., Mimnaugh, E. G., Rosser, M. F. N., Nicchitta, C. V., Marcu, M. G., Yarden, Y., & Neckers, L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006864200 · Cited by 350 · 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., Krishna, P., & Pratt, W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.21213 · Cited by 288 · see citing works
Self-citationNimmanapalli, R., Fuino, L., Bali, P., Gasparetto, M., Glozak, M. A., Tao, J., Moscinski, L. C., Smith, C. A., Wu, J., Jove, R., et al. (2003) · PubMed · Cited by 276 · see citing works
Self-citationWhitesell, L. J., & Cook, P. (1996) · Molecular Endocrinology · doi:10.1210/mend.10.6.8776730 · Cited by 263 · see citing works
Johnson, J. L., & Toft, D. O. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31487-4 · Cited by 229 · see citing works
Self-citationActive maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm
Verdel, A., Curtet, S., Brocard, M.-P., Rousseaux, S., Lemercier, C., Yoshida, M., & Khochbin, S. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00542-x · Cited by 224 · see citing works
Self-citationCadepond, F., Schweizer-Groyer, G., Segard-Maurel, I., Jibard, N., Hollenberg, S. M., Giguère, V., Evans, R. M., & Baulieu, E. E. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)67673-8 · Cited by 161 · see citing works
Morishima, Y., Kanelakis, K. C., Murphy, P. J. M., Lowe, E. R., Jenkins, G. J., Osawa, Y., Sunahara, R. K., & Pratt, W. B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309814200 · Cited by 97 · see citing works
Self-citationAcK-knowledge Reversible Acetylation
Cohen, T., & Yao, T. (2004) · Science s STKE · doi:10.1126/stke.2452004pe42 · Cited by 51 · see citing works
Self-citationKomatsu, Y., Yukutake, Y., & Yoshida, M. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(02)00500-8 · Cited by 14 · see citing works
Self-citation
Flagged first, then by citations
2 of the 25 references couldn’t be matched to a known paper.
Cited by
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Anticancer activities of histone deacetylase inhibitors
Bolden, J. E., Peart, M. J., & Johnstone, R. W. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2133 · Cited by 2,919 · see citing works
Haberland, M., Montgomery, R. L., & Olson, E. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2485 · Cited by 2,541 · see citing works
Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
Minucci, S., & Pelicci, P. G. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1779 · Cited by 2,211 · see citing works
Energy Metabolism in the Liver
Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,258 · 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
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
Acetylation and deacetylation of non-histone proteins
Glozak, M. A., Sengupta, N., Zhang, X., & Seto, E. (2005) · Gene · doi:10.1016/j.gene.2005.09.010 · Cited by 1,584 · see citing works
Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
Falkenberg, K. J., & Johnstone, R. W. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4360 · Cited by 1,564 · see citing works
Histone deacetylase inhibitors: molecular mechanisms of action
Xu, W. S., Parmigiani, R. B., & Marks, P. A. (2007) · Oncogene · doi:10.1038/sj.onc.1210620 · Cited by 1,542 · see citing works
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
Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.026 · Cited by 1,487 · see citing works
Nakahata, Y., Kaluzova, M., Grimaldi, B., Sahar, S., Hirayama, J., Chen, D., Guarente, L. P., & Sassone-Corsi, P. (2008) · Cell · doi:10.1016/j.cell.2008.07.002 · Cited by 1,427 · see citing works
New and emerging HDAC inhibitors for cancer treatment
West, A. C., & Johnstone, R. W. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69738 · Cited by 1,404 · see citing works
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327 · see citing works
Functions and mechanisms of non-histone protein acetylation
Narita, T., Weinert, B. T., & Choudhary, C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0081-3 · Cited by 1,232 · see citing works
The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men
Yang, X., & Seto, E. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2346 · Cited by 1,239 · see citing works
HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS.
Pandey, U. B., Nie, Z., Batlevi, Y., McCray, B. A., Ritson, G. P., Nedelsky, N. B., Schwartz, S. L., DiProspero, N. A., Knight, M. A., Schuldiner, O., et al. (2007) · Nature · doi:10.1038/nature05853 · Cited by 1,234 · see citing works
Self-citationHistone Deacetylase Inhibitors: Overview and Perspectives
Dokmanovic, M., Clarke, C., & Marks, P. A. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-07-0324 · Cited by 1,173 · see citing works
HDAC family: What are the cancer relevant targets?
Witt, O., Deubzer, H. E., Milde, T., & Oehme, I. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.08.016 · Cited by 1,069 · see citing works
Histone deacetylases and cancer
Glozak, M. A., & Seto, E. (2007) · Oncogene · doi:10.1038/sj.onc.1210610 · Cited by 1,031 · see citing works
Lysine Acetylation: Codified Crosstalk with Other Posttranslational Modifications
Yang, X.-J., & Seto, E. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.07.002 · Cited by 1,006 · see citing works
Post-translational modifications in signal integration
Deribe, Y. L., Pawson, T., & Dikic, I. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1842 · Cited by 876 · see citing works
Histone Deacetylase Inhibitors in Cancer Therapy
Lane, A. A., & Chabner, B. A. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.1291 · Cited by 880 · see citing works
Glucocorticoid resistance in inflammatory diseases
Barnes, P. J., & Adcock, I. M. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60326-3 · Cited by 983 · see citing works
Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A
Butler, K. V., Kalin, J., Brochier, C., Vistoli, G., Langley, B., & Kozikowski, A. P. (2010) · Journal of the American Chemical Society · doi:10.1021/ja102758v · Cited by 801 · see citing works
HDAC6 Modulates Cell Motility by Altering the Acetylation Level of Cortactin
Zhang, X. M., Yuan, Z., Zhang, Y., Yong, S., Salas-Burgos, A., Koomen, J. M., Olashaw, N., Parsons, J. T., Yang, X., Dent, S., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.033 · Cited by 731 · see citing works
Self-citationHDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin.
Iwata, A., Riley, B. E., Johnston, J. A., & Kopito, R. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508786200 · Cited by 719 · see citing works
Therapeutic application of histone deacetylase inhibitors for central nervous system disorders
Kazantsev, A. G., & Thompson, L. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2681 · Cited by 715 · see citing works
HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics
Gallinari, P., Marco, S. D., Jones, P., Pallaoro, M., & Steinkühler, C. (2007) · Cell Research · doi:10.1038/sj.cr.7310149 · Cited by 678 · see citing works
Acetylation of non-histone proteins modulates cellular signalling at multiple levels
Spange, S., Wagner, T., Heinzel, T., & Krämer, O. H. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.08.027 · Cited by 665 · see citing works
Hieronymus, H., Lamb, J., Ross, K. N., Peng, X. P., Clement, C. C., Rodina, A., Nieto, M., Du, J., Stegmaier, K., Raj, S. M., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.09.005 · Cited by 616 · see citing works
Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally
Zhang, Y., Kwon, S., Yamaguchi, T., Cubizolles, F., Rousseaux, S., Kneissel, M., Cao, C., Li, N., Cheng, H.-L., Chua, K., et al. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01154-06 · Cited by 559 · see citing works
Histone deacetylases as regulators of inflammation and immunity
Shakespear, M. R., Halili, M. A., Irvine, K. M., Fairlie, D. P., & Sweet, M. J. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.04.001 · Cited by 546 · see citing works
Wandinger, S. K., Richter, K., & Büchner, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800007200 · Cited by 548 · see citing works
Glucocorticosteroids: current and future directions
Barnes, P. J. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01199.x · Cited by 534 · see citing works
Histone deacetylase 6 structure and molecular basis of catalysis and inhibition
Hai, Y., & Christianson, D. W. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2134 · Cited by 521 · see citing works
“25 Other HDAC6 substrates include Hsp90 26 and the microtubule-associated protein Tau, implicating HDAC6 in the pathology of Alzheimer’s disease.”
Heat shock proteins: essential proteins for apoptosis regulation
Lanneau, D., Brunet, M., Frisan, E., Solary, É., Fontenay, M., & Garrido, C. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00273.x · Cited by 502 · see citing works
Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target
Infantino, V., Santarsiero, A., Convertini, P., Todisco, S., & Iacobazzi, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115703 · Cited by 510 · 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
The Hsp90 molecular chaperone: an open and shut case for treatment
Pearl, L. H., Prodromou, C., & Workman, P. (2008) · Biochemical Journal · doi:10.1042/bj20071640 · Cited by 447 · 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
Structure, Function and Regulation of the Hsp90 Machinery
Büchner, J., & Li, J. (2013) · Biomedical Journal · doi:10.4103/2319-4170.113230 · Cited by 421 · see citing works
Marzec, M., Eletto, D., & Argon, Y. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.10.013 · Cited by 416 · see citing works
An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function
Scroggins, B. T., Robzyk, K., Wang, D., Marcu, M. G., Tsutsumi, S., Beebe, K., Cotter, R. J., Felts, S., Toft, D., Karnitz, L., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2006.12.008 · Cited by 413 · see citing works
Self-citationRatman, D., Vanden Berghe, W., Dejager, L., Libert, C., Tavernier, J., Beck, I. M., & De Bosscher, K. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.12.014 · Cited by 411 · see citing works
Kwon, S., Zhang, Y., & Matthias, P. (2007) · Genes & Development · doi:10.1101/gad.461107 · Cited by 402 · see citing works
HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination
Boyault, C., Sadoul, K., Pabion, M., & Khochbin, S. (2007) · Oncogene · doi:10.1038/sj.onc.1210614 · Cited by 397 · see citing works
Histone deacetylase 6 interacts with the microtubule‐associated protein tau
Ding, H., Dolan, P. J., & Johnson, G. V. W. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05564.x · Cited by 387 · see citing works
Energy Metabolism in the Liver
Rui, L. (2014) · Comprehensive physiology · doi:10.1002/j.2040-4603.2014.tb00548.x · Cited by 382 · see citing works
Aldana-Masangkay, G. I., & Sakamoto, K. M. (2010) · BioMed Research International · doi:10.1155/2011/875824 · Cited by 375 · see citing works
Histone Deacetylase Inhibitors: From Bench to Clinic
Paris, M., Porcelloni, M., Binaschi, M., & Fattori, D. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm7011408 · Cited by 373 · see citing works
Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics
Ali, I., Conrad, R. J., Verdin, E. M., & Ott, M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00181 · Cited by 366 · see citing works
HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregatesPreprint
Boyault, C., Zhang, Y., Fritah, S., Caron, C., Gilquin, B., Kwon, S. H., Garrido, C., Yao, T., Vourc’h, C., Matthias, P., et al. (2007) · Genes & Development · doi:10.1101/gad.436407 · Cited by 370 · see citing works
Self-citationPhysical and Functional HAT/HDAC Interplay Regulates Protein Acetylation Balance
Peserico, A., & Simone, C. (2010) · BioMed Research International · doi:10.1155/2011/371832 · Cited by 362 · see citing works
Targeting the correct HDAC(s) to treat cognitive disorders
Fischer, A., Sananbenesi, F., Mungenast, A. E., & Tsai, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.003 · Cited by 355 · see citing works
The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy
Albadari, N. G., Deng, S., & Li, W. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1613370 · Cited by 351 · see citing works
Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes
Li, Y., Shin, D., & Kwon, S. H. (2012) · FEBS Journal · doi:10.1111/febs.12079 · Cited by 346 · see citing works
Histone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapy
Carew, J. S., Giles, F. J., & Nawrocki, S. T. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.037 · Cited by 421 · see citing works
Calderwood, S. K., Murshid, A., & Prince, T. L. (2009) · Gerontology · doi:10.1159/000225957 · Cited by 343 · see citing works
Li, D., Marchenko, N. D., & Moll, U. M. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2011.71 · Cited by 336 · see citing works
Jackson, S. (2012) · Topics in current chemistry · doi:10.1007/128_2012_356 · Cited by 334 · see citing works
AR, the cell cycle, and prostate cancer
Balk, S. P., & Knudsen, K. E. (2008) · Nuclear Receptor Signaling · doi:10.1621/nrs.06001 · Cited by 338 · see citing works
Dual or multi-targeting inhibitors: The next generation anticancer agents
Raghavendra, N. M., Pingili, D., Kadasi, S., Mettu, A., & Prasad, S. V. U. M. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.021 · Cited by 333 · see citing works
Conformational 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
HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation
Parmigiani, R. B., Xu, W., Venta-Perez, G., Erdjument‐Bromage, H., Yaneva, M., Tempst, P., & Marks, P. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803749105 · Cited by 325 · see citing works
Targeting HSP90 for cancer therapy
Mahalingam, D., Swords, R. T., Carew, J. S., Nawrocki, S. T., Bhalla, K. N., & Giles, F. J. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605066 · Cited by 323 · see citing works
Mechanisms and resistance in glucocorticoid control of inflammation
Barnes, P. J. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.02.018 · Cited by 317 · see citing works
Histone deacetylase inhibitors: discovery and development as anticancer agents
Marks, P. A., & Dokmanovic, M. (2005) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.14.12.1497 · Cited by 318 · see citing works
HDAC inhibitor‐based therapies: Can we interpret the code?
New, M. I., Olzscha, H., & Thangue, N. B. L. (2012) · Molecular Oncology · doi:10.1016/j.molonc.2012.09.003 · Cited by 310 · see citing works
Structural insights into HDAC6 tubulin deacetylation and its selective inhibition
Miyake, Y., Keusch, J. J., Wang, L., Saito, M., Hess, D., Wang, X., Melancon, B. J., Helquist, P., Gut, H., & Matthias, P. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2140 · Cited by 315 · see citing works
Qian, D. Z., Kachhap, S. K., Collis, S. J., Verheul, H. M. W., Carducci, M. A., Atadja, P. W., & Пили, Р. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4598 · Cited by 302 · see citing works
The Redox Basis of Epigenetic Modifications: From Mechanisms to Functional Consequences
Cyr, A. R., & Domann, F. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3492 · Cited by 294 · see citing works
Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progressionPreprint
Yamaguchi, T., Cubizolles, F., Zhang, Y., Reichert, N., Kohler, H., Seiser, C., & Matthias, P. (2010) · Genes & Development · doi:10.1101/gad.552310 · Cited by 294 · 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
Polyglutamine diseases: emerging concepts in pathogenesis and therapy
Shao, J., & Diamond, M. I. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm213 · Cited by 284 · see citing works
The clinical development of histone deacetylase inhibitors as targeted anticancer drugs
Marks, P. A. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.510514 · Cited by 282 · see citing works
HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions
Tran, A. D.-A., Marmo, T. P., Salam, A. A., Che, S., Finkelstein, E., Kabarriti, R., Xenias, H. S., Mazitschek, R., Hubbert, C., Kawaguchi, Y., et al. (2007) · Journal of Cell Science · doi:10.1242/jcs.03431 · Cited by 281 · see citing works
Self-citationHistone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
Licciardi, P. V., Ververis, Hiong, & Karagiannis, T. C. (2013) · Biologics · doi:10.2147/btt.s29965 · Cited by 278 · see citing works
Weinert, B. T., Wagner, S., Horn, H., Henriksen, P., Liu, W. R., Olsen, J. V., Jensen, L. J., & Choudhary, C. (2011) · Science Signaling · doi:10.1126/scisignal.2001902 · Cited by 275 · see citing works
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
HDAC6–p97/VCP controlled polyubiquitin chain turnover
Boyault, C., Gilquin, B., Zhang, Y., Rybin, V., Garman, E. F., Meyer‐Klaucke, W., Matthias, P., Müller, C. W., & Khochbin, S. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601210 · Cited by 270 · see citing works
Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification
Duma, D., Jewell, C. M., & Cidlowski, J. A. (2006) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2006.09.009 · Cited by 267 · see citing works
HDAC6 as privileged target in drug discovery: A perspective
Pulya, S., Amin, S. A., Adhikari, N., Biswas, S., Jha, T., & Ghosh, B. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105274 · Cited by 265 · see citing works
Kong, X., Lin, Z., Liang, D., Fath, D., Sang, N., & Caro, J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.6.2019-2028.2006 · Cited by 258 · see citing works
Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions
Li, J.-X., & Cummins, C. L. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00683-6 · Cited by 273 · see citing works
The Cytoplasmic Deacetylase HDAC6 Is Required for Efficient Oncogenic Tumorigenesis
Lee, Y.-S., Lim, K.-H., Guo, X., Kawaguchi, Y., Gao, Y., Barrientos, T., Ordentlich, P., Wang, X.-F., Counter, C. M., & Yao, T.-P. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0188 · Cited by 260 · see citing works
Self-citationTubulin acetylation: responsible enzymes, biological functions and human diseases
Li, L., & Yang, X. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2000-5 · Cited by 257 · see citing works
Histone Deacetylase 6 and Heat Shock Protein 90 Control the Functions of Foxp3 + T-Regulatory Cells
de Zoeten, E. F., Wang, L., Butler, K. V., Beier, U. H., Akimova, T., Sai, H., Bradner, J. E., Mazitschek, R., Kozikowski, A. P., Matthias, P., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05155-11 · Cited by 257 · see citing works
Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis
Hutt, D. M., Herman, D., Rodrigues, A. P. C., Noël, S., Pilewski, J. M., Matteson, J., Hoch, B., Kellner, W. A., Kelly, J. W., Schmidt, A., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.275 · Cited by 253 · see citing works
Yamada, K., Fukao, Y., Hayashi, M., Fukazawa, M., Suzuki, I., & Nishimura, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707168200 · Cited by 248 · see citing works
Hartmann, K., Koenen, M., Schauer, S., Wittig-Blaich, S., Ahmad, M., Baschant, U., & Tuckermann, J. P. (2016) · Physiological Reviews · doi:10.1152/physrev.00011.2015 · Cited by 249 · see citing works
Engin, F., & Hotamışlıgil, G. S. (2010) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2010.01282.x · Cited by 245 · see citing works
Targeting histone deacetylase in cancer therapy
Lin, S.-P., Chen, C., Lin, S.-P., Weng, J., & Chen, C. (2006) · Medicinal Research Reviews · doi:10.1002/med.20056 · Cited by 240 · see citing works
Chen, C., Weng, S., Tseng, P., Lin, H.-P., & Chen, C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505733200 · Cited by 232 · see citing works
Epigenetics and cancer treatment
Kristensen, L. S., Nielsen, H. M., & Hansen, L. L. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.10.011 · Cited by 232 · see citing works
Targeting tumour-supportive cellular machineries in anticancer drug development
Dobbelstein, M., & Moll, U. M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4201 · Cited by 229 · see citing works
Glucocorticoids in T cell development, differentiation and function
Taves, M. D., & Ashwell, J. D. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00464-0 · Cited by 235 · see citing works
Aggresome Formation and Neurodegenerative Diseases: Therapeutic Implications
Chin, L., Olzmann, J. A., & Li, L. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708783330692 · Cited by 227 · see citing works
Histone Deacetylase Inhibitors
Ma, X., Ezzeldin, H. H., & Diasio, R. B. (2009) · Drugs · doi:10.2165/11315680-000000000-00000 · Cited by 226 · see citing works
Inhibitors of histone deacetylase as antitumor agents: A critical review
Mohammed, M., Chandrasekar, M., Jeyapal, G. P., & Nanjan, M. J. (2016) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2016.05.005 · Cited by 227 · see citing works
- Authors
- Kovacs, J. J., Murphy, P. J. M., Gaillard, S., Zhao, X., Wu, J.-T., Nicchitta, C. V., Yoshida, M., Toft, D. O., Pratt, W. B., & Yao, T.-P.
- Affiliations
- Duke University (US)
- University of Michigan (US)
- Japan Science and Technology Agency (JP)
- Mayo Clinic (US)
- Corresponding author
- Yao, Tso-Pang
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 18
- Issue
- 5
- Pages
- 601-607
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1990011854
- Cited by
- 1,153
- References
- 25
- Citations by year
- 2026: 39 · 2025: 49 · 2024: 44 · 2023: 37 · 2022: 55 · 2021: 48 · 2020: 51 · 2019: 50 · 2018: 49 · 2017: 47 · 2016: 63 · 2015: 69 · 2014: 71 · 2013: 69 · 2012: 59
- FWCI
- 20.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- American Cancer Society (RSG-03-147-01-CSM)
- National Institutes of Health (DK31573, CA28010)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- HDAC6, HSP90, HSP90 acetylation, glucocorticoid receptor, p23, steroid hormone receptors, nuclear translocation, transcriptional activation, ligand binding
- MeSH terms
- Histone Deacetylase 6, Acetylation, Animals, Cell Line, Dexamethasone, Glucocorticoids, Histone Deacetylases, Humans, Receptors, Glucocorticoid, Transcription, Genetic, Signal Transduction, HSP90 Heat-Shock Proteins, Mice
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