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HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo
Open accessAbstract
Microtubules are cylindrical cytoskeletal structures found in almost all eukaryotic cell types which are involved in a great variety of cellular processes. Reversible acetylation on the epsilon-amino group of alpha-tubulin Lys40 marks stabilized microtubule structures and may contribute to regulating microtubule dynamics. Yet, the enzymes catalysing this acetylation/deacetylation have remained unidentified until recently. Here we report that beta-tubulin interacts with histone deacetylase-6 (HDAC-6) in a yeast two-hybrid assay and in vitro. We find that HDAC-6 is a micro tubule-associated protein capable of deacetylating alpha-tubulin in vivo and in vitro. HDAC-6's microtubule binding and deacetylation functions both depend on the hdac domains. Overexpression of HDAC-6 in mammalian cells leads to tubulin hypoacetylation. In contrast, inhibition of HDAC-6 function by two independent mechanisms--pharmacological (HDAC inhibitors) or genetic (targeted inactivation of HDAC-6 in embryonic stem cells)--leads to hyperacetylation of tubulin and microtubules. Taken together, our data provide evidence that HDAC-6 might act as a dual deacetylase for tubulin and histones, and suggest the possibility that acetylated non-histone proteins might represent novel targets for pharmacological therapy by HDAC inhibitors.
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“the class IIb isozyme, HDAC6, has been associated with deacetylation of several cytosolic substrates including a -tubulin and p53 (Hubbert et al., 2002; Zhang et al., 2003; Ryu et al., 2017).”
From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Zhang et al., 2003
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Acetylation and deacetylation of non-histone proteins
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“HDAC6 has been shown to function as an α-tubulin deacetylas”
BackgroundHDAC6 Regulates Hsp90 Acetylation and Chaperone-Dependent Activation of Glucocorticoid Receptor
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. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.04.021 · Cited by 1,153
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HEF1-Dependent Aurora A Activation Induces Disassembly of the Primary Cilium
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Histone Deacetylase Inhibitors in Cancer Therapy
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Kazantsev, A. G., & Thompson, L. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2681 · Cited by 727
“In addition to modification of histones, other (non-histone) cellular proteins are substrates for HDACs, and these proteins mediate diverse biological functions via transcriptional-dependent as well as independent mechanism”
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“By contrast, two enzymes that catalyse the opposing reaction — that is, deacetylation — have been recently describe”
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors
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Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally
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“HDAC6, a class II histone deacetylase, is the major enzyme with α-tubulin deacetylating activit”
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“We and others have shown that HDAC6 can deacetylate tubulin as well as the microtubule network in vivo (Hubbert et al. 2002; Matsuyama et al. 2002; Zhang et al. 2003).”
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Boyault, C., Sadoul, K., Pabion, M., & Khochbin, S. (2007) · Oncogene · doi:10.1038/sj.onc.1210614 · Cited by 397
“The discovery of a-tubulin as an HDAC6 substrate (Hubbert et al., 2002; Matsuyama et al., 2002; Zhang et al., 2003) allowed researchers to also include acetylated tubulin in these assays (Haggarty et al.”
BackgroundResultInfluentialSelf-citationHistone 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
“…where it is primarily localized, HDAC6 modulates both microtubule-dependent and actin-dependent cell motility by regulating the acetylation levels of a-tubulin and cortactin, an F-actin-binding protein (Hubbert et al. 2002; Zhang et al. 2003; Matsuyama et al. 2002; Zhang et al. 2007), respectively.”
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“This review will discuss the role of HDAC6 in the pathogenesis and treatment of cancer.”
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Paris, M., Porcelloni, M., Binaschi, M., & Fattori, D. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm7011408 · Cited by 373
HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregatesPreprint
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“2004), is a major cytoplasmic tubulin-deacetylase (Hubbert et al. 2002; Matsuyama et al. 2002; Zhang et al. 2003), and efficiently binds mono- and polyubiquitin (Seigneurin-Berny et al.”
BackgroundTargeting 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 365
Regulation of histone deacetylase activities
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“It is important to note that the primary physiological substrate of HDAC6 and SIRT2 are the cytoplasmic a-tubulin protein and not histones [Hubbert et al., 2002; Matsuyama et al., 2002; North et al., 2003; Zhang et al., 2003].”
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Actin machinery and mechanosensitivity in invadopodia, podosomes and focal adhesions
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“Deacetylation of cortactin by HDAC6 alters its association with actin, thus modulating cell motility (Zhang et al., 2003).”
BackgroundHDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation
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“Inhibition of HDAC6 activity by the specific inhibitor, tubacin, or its down-regulation by siRNA, can increase accumulation of acetylated -tubulin (6, 7) and can alter cellular mobility and can increase acetylated Hsp90 (8–10), inducing client protein degradation.”
BackgroundInsights into the mechanism of microtubule stabilization by Taxol
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Histone deacetylase inhibitors: discovery and development as anticancer agents
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“HDAC6 [49] Mouse ES knockout ES cells Increase in α-tubulin acetylation”
BackgroundInfluentialReview: Tubulin Function, Action of Antitubulin Drugs, and New Drug Development
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“microtubule associated protein, which deacetylates a-tubulin, but the biological significance of this event remains unclear.([22]) Microtubules have been associated with mitochondria accounting for 2% of total cellular tubulin.”
BackgroundStructural 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
Self-citationAcetylation of intrinsically disordered regions regulates phase separation
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Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progressionPreprint
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“HDACs catalyze the deacetylation of lysine residues of histones as well as of an increasing number of other proteins, such as p53 (Luo et al. 2000), HSP90 (Bali et al. 2005; Kovacs et al. 2005), or a-tubulin (Hubbert et al. 2002; Zhang et al. 2003, 2008; for review, see Minucci and Pelicci 2006).”
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HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions
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“Because tubulin is an HDAC6 substrate (Hubbert et al., 2002; Matsuyama et al., 2002; Zhang et al., 2003), acetylated tubulin is one of the hyperacetylated proteins accumulated in HDAC inhibitor-treated cells.”
BackgroundInfluentialHDAC6 Regulates Mitochondrial Transport in Hippocampal Neurons
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“Tubulin is a major substrate of HDAC6; inhibition of HDAC6 can dramatically increase the acetylation of tubulin both in vitro and in vivo [2,3].”
BackgroundHDAC6–p97/VCP controlled polyubiquitin chain turnover
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“Its first identified physiological substrate was however the cytoplasmic protein a-tubulin (Hubbert et al, 2002; Matsuyama et al, 2002; Zhang et al, 2003).”
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HDAC6 as privileged target in drug discovery: A perspective
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Tubulin acetylation: responsible enzymes, biological functions and human diseases
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“Moreover, inactivation of the Hdac6 gene in mouse embryonic stem (ES) cells caused a-tubulin hyperacetylation [63].”
InfluentialRole for Histone Deacetylase 1 in Human Tumor Cell Proliferation
Senese, S., Zaragoza, K., Minardi, S. P., Muradore, I., Ronzoni, S., Passafaro, A., Bernard, L., Draetta, G. F., Alcalay, M., Seiser, C., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00494-07 · Cited by 253
“As expected by published data showing that HDAC6 is the major tubulin deacetylase and that HDAC1 has no specific tubulin deacetylase activity (25, 57), we did not observe changes in tubulin acetylation following siRNA-mediated knockdown of HDAC1 to HDAC3 (data not shown).”
BackgroundTrotta, N., Orso, G., Rossetto, M. G., Daga, A., & Broadie, K. S. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.058 · Cited by 253
Endothelial Barrier and Its Abnormalities in Cardiovascular Disease
Chistiakov, D. A., Orekhov, A. N., & Bobryshev, Y. V. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00365 · Cited by 266
“Histone deacetylase 6 (HDAC6) and SIRT2 are truly responsible for the control of microtubule assembly/disassembly through deacetylation of tubulin (Zhang et al., 2003; Hashimoto-Komatsu et al., 2011). β-adrenergic receptor kinase (BAPK) expressed in ECs and fibroblasts is a recently found activator…”
BackgroundαTAT1 is the major α-tubulin acetyltransferase in mice
Kalebic, N., Sorrentino, S., Perlas, E., Bolasco, G., Martinez, C., & Heppenstall, P. A. (2013) · Nature Communications · doi:10.1038/ncomms2962 · Cited by 241
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Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6
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“DD2, and HA-C-terminus were previously described (Zhang et al., 2003).”
BackgroundInfluentialAssembly and mechanosensory function of focal adhesions: experiments and models
Bershadsky, A. D., Ballestrem, C., Carramusa, L., Zilberman, Y., Gilquin, B., Khochbin, S., Alexandrova, A. Y., Verkhovsky, A. B., Shemesh, T., & Kozlov, M. M. (2005) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2005.11.001 · Cited by 229
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“Finally, to determine whether mDia2 was able to stimulate the deacetylase activity of HDAC6 in cells, we used an in vitro deacetylase assay (Zhang et al., 2003).”
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Epigenetic targeting of histone deacetylase: Therapeutic potential in Parkinson's disease?
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“For example inhibition of HDACs increases the acetylation of α-tubulin, a non-histone target, which increases microtubule stabilisation and axonal transportation aiding the release of BDNF and neuroprotection (Zhang et al., 2003).”
BackgroundIsothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity
Stimson, L., Rowlands, M., Newbatt, Y. M., Smith, N. F., Raynaud, F. I., Rogers, P., Bavetsias, V., Gorsuch, S., Jarman, M., Bannister, A. J., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0135 · Cited by 224
HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
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Histone deacetylase inhibitors as therapeutics for polyglutamine disorders
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“HDAC6 is capable of shuttling between the nucleus and the cytoplasm, although its function seems to be predominantly in the cytoplasm where it deacetylates tubulin and microtubule”
The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility
Pandithage, R., Lilischkis, R., Harting, K., Wolf, A., Jedamzik, B., Lüscher‐Firzlaff, J., Vervoorts, J., Lasonder, E., Kremmer, E., Knöll, B., et al. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200707126 · Cited by 219
“These kinases are critical in regulating distinct steps in transcription, including the phosphorylation of components of the mediator complex and the catalytic subunit of the RNA polymerase II complex ( Zurita and Merino, 2003 ; Marshall and Grana, 2006 ).”
BackgroundAutophagy and microtubules - new story, old players
Mackeh, R., Perdiz, D., Lorin, S., Codogno, P., & Poüs, C. (2013) · Journal of Cell Science · doi:10.1242/jcs.115626 · Cited by 212
“The level of tubulin acetylation depends on the histone deacetylase HDAC6 and the NAD-dependent protein deacetylase sirtuin-2 (SIRT2) (Hubbert et al., 2002; North et al., 2003; Zhang et al., 2003), which have also been shown to active mTOR Lysosome Microtubules Omegasome Centrosome Nucleus Kinesins Kif1Bβ Kif2A Format…”
BackgroundInfluentialKumar, V., Kundu, S., Singh, A., & Singh, S. (2022) · Current Neuropharmacology · doi:10.2174/1570159x19666210609160017 · Cited by 210
“Mut ated Htt Inhi bitio n of casp ase a ctivi ty Nucle ar inc lusion Aggr egati on CRE BC BP/P 300 P/CA F CR F P NRSE REST CoRE ST Ac H BDNF, GDNF Cytoplasm Nuc leus HDAC makes complex with REST mHtt Activa tion of ER K N eu ro de ge ne ra tio n (H D ) & ne ur ol og ic al d iso rd er Class Sub Class Modulat-or Sub Cel…”
BackgroundInfluentialHistone 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
“Indeed, HDAC6 uniquely possesses a microtubule deacetylase activity (22, 31, 60 ).”
BackgroundMaxwell, M. M., Tomkinson, E. M., Nobles, J., Wizeman, J. W., Amore, A. M., Quinti, L., Chopra, V., Hersch, S. M., & Kazantsev, A. G. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr326 · Cited by 209
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 224
Geeraert, C., Ratier, A., Pfisterer, S. G., Perdiz, D., Cantaloube, I., Rouault, A., Pattingre, S., Proikas‐Cezanne, T., Codogno, P., & Poüs, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.091553 · Cited by 222
Yee, A. J., Bensinger, W., Supko, J. G., Voorhees, P. M., Berdeja, J. G., Richardson, P. G. G., Libby, E. N., Wallace, E. E., Birrer, N., Burke, J. N., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30375-8 · Cited by 205
HDAC5 is a novel injury‐regulated tubulin deacetylase controlling axon regeneration
Cho, Y., & Cavalli, V. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.160 · Cited by 204
“In contrast to earlier reports showing that HDAC5 does not deacetylate a -tubulin derived peptides (Zhang et al , 2003), HDAC5 efficiency was comparable to HDAC6 (Figure 5E).”
Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models
Cao, Y., Semanchik, N., Lee, S. H., Somlo, S., Barbano, P. E., Coifman, R. R., & Sun, Z. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911987106 · Cited by 204
Waltregny, D., Glénisson, W., Tran, S. L., North, B. J., Verdin, E. M., Colige, A., & Castronovo, V. (2005) · The FASEB Journal · doi:10.1096/fj.04-2303fje · Cited by 197
Class IIb HDAC6 regulates endothelial cell migration and angiogenesis by deacetylation of cortactin
Kaluza, D., Krøll, J., Gesierich, S., Yao, T., Boon, R. A., Hergenreider, E., Tjwa, M., Rössig, L., Seto, E., Augustin, H. G., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.298 · Cited by 196
HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy
Krukowski, K., Ma, J., Golonzhka, O., Laumet, G. O., Gutti, T., van Duzer, J. H., Mazitschek, R., Jarpe, M. B., Heijnen, C. J., & Kavelaars, A. (2017) · Pain · doi:10.1097/j.pain.0000000000000893 · Cited by 189
“been implicated in the regulation of mitochondrial transport.(22,40,55) In vitro, HDAC6 inhibition increases a-tubulin acetylation and promotes mitochondrial transport in hippocampal neurons.”
Posttranslational Modifications of Tubulin and Cilia
Wloga, D., Joachimiak, E., Louka, P., & Gaertig, J. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028159 · Cited by 183
“ENZYMES IN THE DISASSEMBLY OF CILIA HDAC6 (Hubbert et al. 2003; Zhang et al. 2003) and SIRT2 (North et al. 2003) are two acetylK40 deacetylases that promote disassembly of primary cilia in mammalian cells.”
BackgroundRegulation of CD133 by HDAC6 Promotes β-Catenin Signaling to Suppress Cancer Cell Differentiation
Mak, A. B., Nixon, A. M. L., Kittanakom, S., Stewart, J. M., Chen, G. I., Ćurak, J., Gingras, A., Mazitschek, R., Neel, B. G., Štagljar, I., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.09.016 · Cited by 191
“Unlike other histone deacetylases, HDAC6 is primarily cytoplasmic, associated with microtubules and dynein motors, and directly regulates the acetylation state of α-tubulin at lysine 40 through its deacetylase activity (Hubbert et al., 2002; Zhang et al., 2003, 2006).”
BackgroundHistone 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
“Making use of its second catalytic domain, HDAC6 deacetylates and, thereby, regulates the function of α-tubulin (Hubbert et al. 2002; Zhang et al. 2003) and of molecular chaperone Hsp90 as well as of glucocorticoid receptor (Bali et al.”
BackgroundWickström, S. A., Masoumi, K. C., Khochbin, S., Fässler, R., & Massoumi, R. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.317 · Cited by 178
“It has been suggested earlier that the localization of HDAC6 in the midbody might regulate mitosis by affecting MT dynamics during cytokinesis (Zhang et al, 2003).”
BackgroundHistone Modification in NSCLC: Molecular Mechanisms and Therapeutic Targets
Bajbouj, K., Al-Ali, A., Ramakrishnan, R. K., Saber-Ayad, M. M., & Hamid, Q. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111701 · Cited by 179
Histone modifications and chromatin dynamics: a focus on filamentous fungi
Brosch, G., Loidl, P., & Graessle, S. (2008) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2007.00100.x · Cited by 180
“Because a total of 26 potentially acetylated lysine residues are present in a nucleosome, this overall charge neutralization might weaken the interaction of the core histone octamer with the negatively charged DNA.”
BackgroundMelatonin and sirtuins: A “not-so unexpected” relationship
Mayo, J. C., Sainz, R. M., González Menéndez, P., Cepas, V., Tan, D., & Reiter, R. J. (2017) · Journal of Pineal Research · doi:10.1111/jpi.12391 · Cited by 175
Jochems, J., Boulden, J., Lee, B. G., Blendy, J. A., Jarpe, M. B., Mazitschek, R., van Duzer, J. H., Jones, S. S., & Berton, O. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.207 · Cited by 175
“HDAC6 is a structurally and functionally unique class IIb isoform localized almost exclusively to the cytoplasm (Verdel et al, 2000) that does not appear to deacetylate histones in vivo (Zhang et al, 2003).”
Advances in targeting histone deacetylase for treatment of solid tumors
Shi, M.-Q., Xu, Y., Fu, X., Pan, D., Lu, X., Xiao, Y., & Jiang, Y. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01551-8 · Cited by 181
“In general, HDACs exhibit distinct physiological functions and structural characteristics based on their respective classifications (Table 1) [23–26].”
Backgroundβ1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli
Li, N., Zhang, Y., Naylor, M. J., Schatzmann, F., Maurer, F., Wintermantel, T. M., Schüetz, G., Mueller, U. W., Streuli, C. H., & Hynes, N. E. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600674 · Cited by 168
Neugebauer, R. C., Uciechowska, U., Meier, R., Hruby, H., Valkov, V., Verdin, E. M., Sippl, W., & Jung, M. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm700972e · Cited by 166
Tau – an inhibitor of deacetylase HDAC6 function
Perez, M., Santa‐Maria, I., De Barreda, E. G., Zhu, X., Cuadros, R., Cabrero, J. R., Sanchez‐Madrid, F., Dawson, H. N., Vitek, M. P., Perry, G., et al. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06102.x · Cited by 182
“At least two types of deacetylases act on acetylated tubulin (North et al. 2003; Zhang et al. 2003), the most studied being histone deacetylase 6 (HDAC6) (Zhang et al. 2003).”
BackgroundInfluentialDeacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
Ran, J., Yang, Y., Li, D., Liu, M., & Zhou, J. (2015) · Scientific Reports · doi:10.1038/srep12917 · Cited by 166
A plant dialect of the histone language
Loidl, P. (2004) · Trends in Plant Science · doi:10.1016/j.tplants.2003.12.007 · Cited by 168
Regulation of Histone Acetylation by Autophagy in Parkinson Disease
Park, G., Tan, J., Garcia, G., Kang, Y., Salvesen, G. S., & Zhang, Z. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.675488 · Cited by 162
“HDAC inhibition-induced acetylation of -tubulin stabilizes microtubules and increases axonal transportation leading to BDNF release and neuroprotection (31, 32).”
BackgroundTwo Catalytic Domains Are Required for Protein Deacetylation
Zhang, Y., Gilquin, B., Khochbin, S., & Matthias, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500241200 · Cited by 161
Li, Z., & Zhu, W. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.9067 · Cited by 164
“HDAC6 interacts and deacetylates tubulin [160, 161].”
Role of the Tetradecapeptide Repeat Domain of Human Histone Deacetylase 6 in Cytoplasmic Retention
Bertos, N., Gilquin, B., Chan, G. K. T., Yen, T. J., Khochbin, S., & Yang, X. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408583200 · Cited by 160
Crystal Structure of a Bacterial Class 2 Histone Deacetylase Homologue
Nielsen, T. K., Hildmann, C., Dickmanns, A., Schwienhorst, A., & Ficner, R. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.09.065 · Cited by 157
Carta, S., Tassi, S., Semino, C., Fossati, G., Mascagni, P., Dinarello, C. A., & Rubartelli, A. (2006) · Blood · doi:10.1182/blood-2006-03-014126 · Cited by 151
“Deacetylation of both proteins is mediated by HDAC6, which acts cytoplasmically.(25,26) In addition, α-tubulin is a target of the NADdependent histone deacetylase SIRT2.”
BackgroundAdeegbe, D. O., Liu, Y., Lizotte, P. H., Kamihara, Y., Aref, A. R., Almonte, C. G., Dries, R., Li, Y., Liu, S., Wang, X., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1020 · Cited by 150
“This finding suggests that inhibition of class I HDAC and class II HDAC6 by compounds such as ricolinostat and ACY-241 may affect Treg frequency more so than single classselective agents such as entinostat.”
BackgroundInfluentialDual Targeting of Histone Deacetylase and Topoisomerase II with Novel Bifunctional Inhibitors
Guerrant, W., Patil, V., Canzoneri, J. C., & Oyelere, A. K. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm200799p · Cited by 149
Kim, G.-W., Li, L., Gorbani, M., You, L., & Yang, X.-J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.464792 · Cited by 141
Characterization of the two catalytic domains in histone deacetylase 6
Zou, H., Wu, Y., Navre, M., & Sang, B. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.12.144 · Cited by 144
Liu, Y., Peng, L., Seto, E., Huang, S., & Qiu, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.371120 · Cited by 144
Bates, E. A., Victor, M., Jones, A. K., Shi, Y., & Hart, A. C. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3344-05.2006 · Cited by 149
“For instance, mammalian HDAC6 and Sir2 deacetylate tubulin (Hubbert et al., 2002; Matsuyama et al., 2002; North et al., 2003; Zhang et al., 2003).”
BackgroundHistone deacetylase 11 is an ε-N-Myristoyllysine hydrolase
Moreno-Yruela, C., Galleano, I., Madsen, A. S., & Olsen, C. A. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.04.007 · Cited by 149
Metadata
- Authors
- Zhang, Y., Li, N., Caron, C., Matthias, G., Hess, D., Khochbin, S., & Matthias, P.
- Affiliations
- Friedrich Miescher Institute (CH)
- Inserm (FR)
- Corresponding author
- Matthias, Patrick
- Venue
- The EMBO Journal
- Published
- 2003-03-03
- Volume
- 22
- Issue
- 5
- Pages
- 1168-1179
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC150348
- OpenAlex
- W1979832500
- Cited by
- 740
- References
- 38
- Citations by year
- 2026: 26 · 2025: 20 · 2024: 27 · 2023: 37 · 2022: 24 · 2021: 29 · 2020: 35 · 2019: 29 · 2018: 32 · 2017: 22 · 2016: 39 · 2015: 35 · 2014: 26 · 2013: 45 · 2012: 41
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Harvard University
- University of California, San Francisco
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- histone deacetylase, tubulin deacetylation, alpha-tubulin, beta-tubulin, microtubules, tubulin acetylation, microtubule dynamics, histone deacetylase inhibitors, non-histone protein acetylation, cytoskeleton
- MeSH terms
- Histone Deacetylase 6, Acetylation, Animals, Cattle, Chromatography, High Pressure Liquid, Embryo, Mammalian, Histone Deacetylases, Humans, Kidney, Microtubules, Peptides, Protein Binding, Stem Cells, Tubulin, 3T3 Cells, Paclitaxel, Protein Structure, Tertiary, Two-Hybrid System Techniques, Mice
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