Inhibition of Histone Deacetylase 6 Acetylates and Disrupts the Chaperone Function of Heat Shock Protein 90
Open accessAbstract
The hydroxamic acid (HAA) analogue pan-histone deacetylase (HDAC) inhibitors (HDIs) LAQ824 and LBH589 have been shown to induce acetylation and inhibit the ATP binding and chaperone function of heat shock protein (HSP) 90. This promotes the polyubiquitylation and degradation of the pro-growth and pro-survival client proteins Bcr-Abl, mutant FLT-3, c-Raf, and AKT in human leukemia cells. HDAC6 is a member of the class IIB HDACs. It is predominantly cytosolic, microtubule-associated alpha-tubulin deacetylase that is also known to promote aggresome inclusion of the misfolded polyubiquitylated proteins. Here we demonstrate that in the Bcr-abl oncogene expressing human leukemia K562 cells, HDAC6 can be co-immunoprecipitated with HSP90, and the knock-down of HDAC6 by its siRNA induced the acetylation of HSP90 and alpha-tubulin. Depletion of HDAC6 levels also inhibited the binding of HSP90 to ATP, reduced the chaperone association of HSP90 with its client proteins, e.g. Bcr-Abl, and induced polyubiquitylation and partial depletion of Bcr-Abl. Conversely, the ectopic overexpression of HDAC6 inhibited LAQ824-induced acetylation of HSP90 and alpha-tubulin and reduced LAQ824-mediated depletion of Bcr-Abl, AKT, and c-Raf. Collectively, these findings indicate that HDAC6 is also an HSP90 deacetylase. Targeted inhibition of HDAC6 leads to acetylation of HSP90 and disruption of its chaperone function, resulting in polyubiquitylation and depletion of pro-growth and pro-survival HSP90 client proteins including Bcr-Abl. Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors.
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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 [17]
HDAC6 is the deacetylase for a diverse set of substrates involved in tumourigenesis, such as HSP90, α-tubulin, cortactin and peroxiredoxins.
“HDAC6 was shown to be the deacetylase for a diverse set of substrates involved in tumourigenesis, such as HSP90, α-tubulin, cortactin and peroxiredoxins”
From A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth (2013) · cites this paper as Bali et al, 2005
HDAC6 knockout in mice does not lead to embryonic lethality.
“HDAC6 knockout in mice does not lead to embryonic lethality”
From A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth (2013) · cites this paper as Bali et al, 2005
Inhibition of HDAC6 is believed not to be associated with severe toxicity.
“unlike other HDACs, inhibition of HDAC6 is believed not to be associated with severe toxicity”
From A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth (2013) · cites this paper as Bali et al, 2005
Cites
Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein
Hartl, F. U., & Hayer-Hartl, M. K. (2002) · Science · doi:10.1126/science.1068408 · Cited by 3,335 · see citing works
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
Histone deacetylases and cancer: causes and therapies
Marks, P. A., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T., & Kelly, W. K. (2001) · Nature reviews. Cancer · doi:10.1038/35106079 · Cited by 1,866 · see citing works
Pratt, W., & Toft, D. (2003) · Experimental biology and medicine · doi:10.1177/153537020322800201 · Cited by 1,539 · see citing works
Kawaguchi, 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
Stebbins, C. E., Russo, A. A., Schneider, C. B., Rosen, N. X., Hartl, F. U., & Pavletich, N. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80203-2 · Cited by 1,370 · see citing works
Felsenfeld, G., & Groudine, M. T. (2003) · Nature · doi:10.1038/nature01411 · Cited by 1,153 · 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
Role of the Heat Shock Response and Molecular Chaperones in Oncogenesis and Cell Death
Jolly, C. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.19.1564 · Cited by 1,049 · 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
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
Khorasanizadeh, S. (2004) · Cell · doi:10.1016/s0092-8674(04)00044-3 · Cited by 672 · see citing works
Class II histone deacetylases: versatile regulators
Verdin, E., Dequiedt, F., & Kasler, H. G. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00073-8 · Cited by 664 · see citing works
Histone deacetylases, transcriptional control, and cancer
Cress, W. D., & Seto, E. (2000) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(200007)184:1 · Cited by 619 · see citing works
Self-citationHeat shock protein 90 as a molecular target for cancer therapeutics
Isaacs, J. S., Xu, W., & Neckers, L. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00029-1 · Cited by 575 · 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
Activation of the ATPase Activity of Hsp90 by the Stress-Regulated Cochaperone Aha1
Panaretou, B., Siligardi, G., Meyer, P., Maloney, A., Sullivan, J. K., Singh, S., Millson, S. H., Clarke, P. A., Naaby‐Hansen, S., Stein, R. C., et al. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00785-2 · Cited by 544 · see citing works
Meyer, P., Prodromou, C., Hu, B., Vaughan, C., Roe, S. M., Panaretou, B., Piper, P. W., & Pearl, L. H. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00065-0 · Cited by 491 · see citing works
Histone deacetylase inhibitors in cancer therapy
Johnstone, R. W., & Licht, J. D. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00165-x · Cited by 448 · see citing works
Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein
Taylor, J. P. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg074 · Cited by 425 · see citing works
Signaling Network Model of Chromatin
Schreiber, S. L., & Bernstein, B. (2002) · Cell · doi:10.1016/s0092-8674(02)01196-0 · Cited by 395 · see citing works
Pei, X., Dai, Y., & Grant, S. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0561 · Cited by 381 · 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
George, P., Bali, P., Annavarapu, S., Scuto, A., Fiskus, W. C., Guo, F., Sigua, C. A., Sondarva, G. V., Moscinski, L. C., Atadja, P. W., et al. (2004) · Blood · doi:10.1182/blood-2004-09-3413 · Cited by 327 · see citing works
Self-citationAltered Hsp90 function in cancer: A unique therapeutic opportunity
Bagatell, R., & Whitesell, L. J. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1021.3.8 · Cited by 301 · see citing works
HDAC6 Expression Is Correlated with Better Survival in Breast Cancer
Zhang, Z., Yamashita, H., Toyama, T., Sugiura, H., Omoto, Y., Ando, Y., Mita, K., Hamaguchi, M., Hayashi, S., & Iwase, H. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0455 · Cited by 295 · see citing works
Nimmanapalli, 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-citationBagatell, R., Paine-Murrieta, G. D., Taylor, C. W., Pulcini, E. J., Akinaga, S., Benjamin, I. J., & Whitesell, L. J. (2000) · PubMed · Cited by 270 · see citing works
Fang, G., Kim, C. N., Perkins, C. L., Nimmanapalli, R., Winton, E. F., Wittmann, S., & Bhalla, K. N. (2000) · Blood · doi:10.1182/blood.v96.6.2246 · Cited by 268 · see citing works
Self-citationFuino, L., Bali, P., Wittmann, S., Donapaty, S., Guo, F., Yamaguchi, H., Wang, H., Atadja, P. W., & Bhalla, K. N. (2003) · PubMed · Cited by 261 · see citing works
Self-citationNimmanapalli, R., O’Bryan, E., & Bhalla, K. N. (2001) · PubMed · Cited by 243 · see citing works
Self-citationHook, S. S., Orian, A., Cowley, S. M., & Eisenman, R. N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172511699 · Cited by 229 · see citing works
Zhang, X. M., Ozawa, Y., Lee, H., Wen, Y., Tan, T., Wadzinski, B. E., & Seto, E. (2005) · Genes & Development · doi:10.1101/gad.1286005 · Cited by 222 · see citing works
Self-citationMimnaugh, E. G., Xu, W., Vos, M. D., Yuan, X., Isaacs, J. S., Bisht, K. S., Gius, D. R., & Neckers, L. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.551.3.5 · Cited by 211 · see citing works
Guo, F., Sigua, C. A., Tao, J., Bali, P., George, P., Li, Y.-Q., Wittmann, S., Moscinski, L. C., Atadja, P. W., & Bhalla, K. N. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2629 · Cited by 202 · see citing works
Self-citationAnomalous expression of the HLA-DR alpha and beta chains in ovarian and other cancers
Rangel, L. B. A., Agarwal, R., Sherman‐Baust, C. A., Coelho, V. D. M., Pizer, E. S., Ji, H., Taub, D. D., & Morin, P. J. (2004) · Cancer Biology & Therapy · doi:10.4161/cbt.3.10.1142 · Cited by 166 · see citing works
Bali, P., George, P., Cohen, P. S., Tao, J., Guo, F., Sigua, C. A., Vishvanath, A., Scuto, A., Annavarapu, S., Fiskus, W. C., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0210 · Cited by 127 · see citing works
Self-citationGeorge, P., Bali, P., Cohen, P. S., Tao, J., Guo, F., Sigua, C. A., Vishvanath, A., Fiskus, W. C., Scuto, A., Annavarapu, S., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0006 · Cited by 124 · see citing works
Self-citationNimmanapalli, R., O’Bryan, E., Huang, M., Bali, P., Burnette, P. K., Loughran, T. P., Tepperberg, J. H., Jove, R., & Bhalla, K. N. (2002) · PubMed · Cited by 112 · see citing works
Self-citationMhaka, A. M., Gady, A. M., Rosen, D. M., Lo, K.-M., Gillies, S. D., & Denmeade, S. R. (2004) · Cancer Biology & Therapy · doi:10.4161/cbt.3.6.846 · Cited by 105 · see citing works
Dissection of the Contribution of Individual Domains to the ATPase Mechanism of Hsp90
Wegele, H., Muschler, P., Bunck, M., Reinstein, J., & Büchner, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305751200 · Cited by 67 · see citing works
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Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
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Schopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540 · see citing works
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Self-citationHistone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
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West, A. C., & Johnstone, R. W. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69738 · Cited by 1,404 · see citing works
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Yang, X., & Seto, E. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2346 · Cited by 1,239 · 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
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Self-citationLysine 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
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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
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HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics
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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
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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
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Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes
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Catley, L. P., Weisberg, E., Kiziltepe, T., Tai, Y., Hideshima, T., Neri, P., Tassone, P., Atadja, P. W., Chauhan, D., Munshi, N. C., et al. (2006) · Blood · doi:10.1182/blood-2006-04-016055 · Cited by 335 · see citing works
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HDAC inhibitor‐based therapies: Can we interpret the code?
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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
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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
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
Self-citationHistone acetylation in gene regulation
Verdone, L. (2006) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/ell028 · Cited by 245 · see citing works
Richon, V. M. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603463 · Cited by 240 · see citing works
Arts, J., King, P., Marin, A., Floren, W., Belin, A., Janssen, L., Pilatte, I., Roux, B., Decrane, L., Gilissen, R., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0547 · Cited by 231 · see citing works
Badros, A. Z., Burger, A. M., Philip, S., Niesvizky, R., Kolla, S. S., Goloubeva, O. G., Harris, C., Zwiebel, J. A., Wright, J. J., Espinoza‐Delgado, I., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2850 · Cited by 231 · see citing works
Sydor, J. R., Normant, E., Pien, C. S., Porter, J. R., Ge, J., Grenier, L., Pak, R. H., Ali, J. A., Dembski, M. S., Hudak, J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608372103 · Cited by 231 · 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
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
HDACs and HDAC inhibitors in colon cancer
Mariadason, J. M. (2008) · Epigenetics · doi:10.4161/epi.3.1.5736 · Cited by 226 · see citing works
Regulation of protein turnover by acetyltransferases and deacetylases
Sadoul, K., Boyault, C., Pabion, M., & Khochbin, S. (2007) · Biochimie · doi:10.1016/j.biochi.2007.06.009 · Cited by 223 · see citing works
Histone deacetylase 10 promotes autophagy-mediated cell survival
Oehme, I., Linke, J.-P., Böck, B. C., Milde, T., Lodrini, M., Hartenstein, B., Wiegand, I., Eckert, C., Roth, W., Kool, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300113110 · Cited by 221 · see citing works
Role of Acetylation and Extracellular Location of Heat Shock Protein 90α in Tumor Cell Invasion
Yang, Y., Rao, R., Shen, J., Tang, Y., Fiskus, W. C., Nechtman, J., Atadja, P. W., & Bhalla, K. N. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0644 · Cited by 221 · see citing works
Self-citationTargeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy
Singh, A. K., Bishayee, A., & Pandey, A. K. (2018) · Nutrients · doi:10.3390/nu10060731 · Cited by 224 · see citing works
Autophagy inhibition enhances vorinostat‐induced apoptosis via ubiquitinated protein accumulation
Carew, J. S., Medina, E. C., Esquivel, J., Mahalingam, D., Swords, R. T., Kelly, K. R., Zhang, H., Huang, P., Mita, A. C., Mita, M. M., et al. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00832.x · Cited by 219 · see citing works
Histone deacetylase inhibitors and cell death
Zhang, J., & Zhong, Q. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1656-6 · Cited by 216 · see citing works
Hsp90, an unlikely ally in the war on cancer
Barrott, J. J., & Haystead, T. (2013) · FEBS Journal · doi:10.1111/febs.12147 · Cited by 218 · see citing works
Histone deacetylase inhibitors as therapeutics for polyglutamine disorders
Butler, R. K., & Bates, G. P. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn1989 · Cited by 212 · see citing works
Histone Deacetylase 6 Regulates Growth Factor-Induced Actin Remodeling and Endocytosis
Gao, Y., Hubbert, C. C., Lu, J., Lee, Y.-S., Lee, J., & Yao, T. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00393-07 · Cited by 209 · see citing works
The ins and outs of tubulin acetylation: More than just a post-translational modification?
Perdiz, D., Mackeh, R., Poüs, C., & Baillet, A. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.10.014 · Cited by 206 · see citing works
Post-translational modifications of Hsp90 and translating the chaperone code
Backe, S. J., Sager, R., Woodford, M. R., Makedon, A. M., & Mollapour, M. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.011833 · Cited by 208 · see citing works
Namdar, M., Perez, G., Ngo, L., & Marks, P. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013754107 · Cited by 207 · see citing works
Yang, Y., Fiskus, W. C., Yong, B., Atadja, P. W., Takahashi, Y., Pandita, T. K., Wang, H., & Bhalla, K. N. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217692110 · Cited by 204 · see citing works
Self-citationTargeting HDACs: A Promising Therapy for Alzheimer's Disease
Xu, K., Dai, X., Huang, H., & Jiang, Z.-F. (2011) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2011/143269 · Cited by 206 · see citing works
Pratt, W. B., Morishima, Y., Peng, H., & Osawa, Y. (2010) · Experimental Biology and Medicine · doi:10.1258/ebm.2009.009250 · Cited by 201 · see citing works
Multiple roles of class I HDACs in proliferation, differentiation, and development
Reichert, N., Choukrallah, M.-A., & Matthias, P. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0921-9 · Cited by 194 · see citing works
Beckers, T. L., Burkhardt, C., Wieland, H., Gimmnich, P., Ciossek, T., Maier, T. M., & Sanders, K. (2007) · International Journal of Cancer · doi:10.1002/ijc.22751 · Cited by 191 · see citing works
Epi-drugs to fight cancer: From chemistry to cancer treatment, the road ahead
Mai, A., & Altucci, L. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.08.020 · Cited by 190 · see citing works
Chaperoning steroid hormone action
Picard, D. (2006) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2006.06.003 · Cited by 186 · see citing works
Rao, R., Fiskus, W. C., Yang, Y., Lee, P., Joshi, R., Fernandez, P., Mandawat, A., Atadja, P. W., Bradner, J. E., & Bhalla, K. N. (2008) · Blood · doi:10.1182/blood-2008-03-143644 · Cited by 189 · see citing works
Self-citationHistone deacetylase inhibitors: A chemical genetics approach to understanding cellular functions
Marks, P. A. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2010.05.008 · Cited by 189 · see citing works
Lo, P., & Sukumar, S. V. (2008) · Pharmacogenomics · doi:10.2217/14622416.9.12.1879 · Cited by 183 · see citing works
Chaperone-dependent stabilization and degradation of p53 mutants
Müller, P., Hrstka, R., Coomber, D., Lane, D. P., & Vojtěšek, B. (2008) · Oncogene · doi:10.1038/sj.onc.1211010 · Cited by 183 · see citing works
Histone deacetylases—an important class of cellular regulators with a variety of functions
Hildmann, C., Riester, D., & Schwienhorst, A. (2007) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-007-0911-2 · Cited by 182 · see citing works
Welsbie, D. S., Xu, J., Chen, Y., Borsu, L. A., Scher, H. I., Rosen, N. X., & Sawyers, C. L. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2216 · Cited by 182 · see citing works
Wang, Y., Fiskus, W. C., Chong, D. G., Buckley, K. M., Natarajan, K., Rao, R., Joshi, A., Balusu, R., Koul, S., Chen, J., et al. (2009) · Blood · doi:10.1182/blood-2009-05-222133 · Cited by 177 · see citing works
Self-citationLi, Y., Zhang, T., Schwartz, S. J., & Sun, D. (2009) · Drug Resistance Updates · doi:10.1016/j.drup.2008.12.002 · Cited by 176 · see citing works
A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activityPreprint
Li, Y., Kao, G. D., Garcia, B. A., Shabanowitz, J., Hunt, D. F., Qin, J., Phelan, C. A., & Lazar, M. A. (2006) · Genes & Development · doi:10.1101/gad.1455006 · Cited by 175 · see citing works
Mayer, M. P., & Breton, L. L. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.022 · Cited by 176 · see citing works
HDAC6 Is Required for Epidermal Growth Factor-induced β-Catenin Nuclear Localization
Li, Y., Zhang, X., Polakiewicz, R. D., Yao, T., & Comb, M. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.c700185200 · Cited by 174 · see citing works
Gibbs, A., Schwartzman, J. A., Deng, V., & Alumkal, J. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908908106 · Cited by 174 · see citing works
Parbin, S., Kar, S., Shilpi, A., Sengupta, D., Deb, M., Rath, S. K., & Patra, S. K. (2013) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155413506582 · Cited by 172 · see citing works
Development of vorinostat: Current applications and future perspectives for cancer therapy
Richon, V. M., Garcia-Vargas, J. E., & Hardwick, J. S. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.01.002 · Cited by 169 · see citing works
p53-Mediated Molecular Control of Autophagy in Tumor Cells
Mrakovcic, M., & Fröhlich, L. F. (2018) · Biomolecules · doi:10.3390/biom8020014 · Cited by 169 · see citing works
Gao, Y., Hubbert, C. C., & Yao, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.042754 · Cited by 167 · see citing works
Regulation of the mammalian heat shock factor 1
Naidu, S. D., & Dinkova‐Kostova, A. T. (2017) · FEBS Journal · doi:10.1111/febs.13999 · Cited by 159 · see citing works
Comprehensive lysine acetylomes emerging from bacteria to humans
Kim, G.-W., & Yang, X. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.10.001 · Cited by 165 · see citing works
Role of Heat Shock Proteins (HSP70 and HSP90) in Viral Infection
Lubkowska, A., Pluta, W. W., Strońska-Pluta, A., & Lalko, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179366 · Cited by 168 · see citing works
Differentiation therapy of acute myeloid leukemia: past, present and future
Petrie, K. R., Zelent, A., & Waxman, S. (2009) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283257aee · Cited by 161 · see citing works
Sabnis, G. J., Goloubeva, O. G., Chumsri, S., Nguyen, N., Sukumar, S. V., & Brodie, A. M. H. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2458 · Cited by 160 · see citing works
- Authors
- Bali, P., Pranpat, M., Bradner, J., Balasis, M., Fiskus, W., Guo, F., Rocha, K., Kumaraswamy, S., Boyapalle, S., Atadja, P., Seto, E., & Bhalla, K.
- Affiliations
- Moffitt Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- Novartis (United States) (US)
- Corresponding author
- Bhalla, Kapil
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 280
- Issue
- 29
- Pages
- 26729-26734
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2151445954
- Cited by
- 755
- References
- 42
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 10 · 2023: 9 · 2022: 23 · 2021: 21 · 2020: 38 · 2019: 33 · 2018: 32 · 2017: 28 · 2016: 34 · 2015: 40 · 2014: 45 · 2013: 42 · 2012: 47
- FWCI
- 19.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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, LAQ824, panobinostat, BCR-ABL, alpha-tubulin deacetylation, polyubiquitination, Hsp90 client proteins, Akt, Raf-1, leukemia, K562 cells, proteasome inhibitors, siRNA knockdown
- MeSH terms
- Histone Deacetylase 6, Panobinostat, Acetylation, Antineoplastic Agents, Enzyme Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Indoles, Leukemia, Neoplasm Proteins, Protein Binding, Molecular Chaperones, HSP90 Heat-Shock Proteins, K562 Cells, Ubiquitin, Histone Deacetylase Inhibitors
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