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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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HDAC6 and SIRT2 Regulate the Acetylation State and Oncogenic Activity of Mutant K-RAS
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BackgroundMicrotubule Deacetylases, SirT2 and HDAC6, in the Nervous System
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BackgroundBack to the tubule: microtubule dynamics in Parkinson’s disease
Pellegrini, L., Wetzel, A., Grannò, S., Heaton, G., & Harvey, K. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2351-6 · Cited by 147
“HDAC6 mediated a-tubulin deacetylation was also observed in mouse embryonic stem cells within the same study [91].”
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BackgroundHDAC6 α-tubulin deacetylase: A potential therapeutic target in neurodegenerative diseases
Li, G., Jiang, H., Chang, M., Xie, H., & Hu, L. (2011) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2011.02.017 · Cited by 141
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BackgroundHDAC inhibitor-based therapies and haematological malignancy
Stimson, L., Wood, V. H. J., Khan, O. A., Fotheringham, S. A., & Thangue, N. B. L. (2009) · Annals of Oncology · doi:10.1093/annonc/mdn792 · Cited by 136
“HDAC6, located in the cytoplasm where it acts as an a-tubulin deacetylase [20], may participate in regulating cell viability in response to misfolded proteins [21].”
BackgroundLaw, B. M. H., Spain, V. A., Leinster, V. H. L., Chia, R., Beilina, A. G., Cho, H. J., Taymans, J., Urban, M. K., Sancho, R. M., Ramírez, M. B., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.507913 · Cited by 135
“In mammals, the major enzyme catalyzing tubulin acetylation is the -tubulin Lys-40 acetyltransferase (also known as MEC-17) (47, 54), whereas deacetylation is carried out by two enzymes, histone deacetylase 6 (HDAC6) (48, 55, 56) and sirtuin2 (SIRT2) (57).”
BackgroundCytoskeletal Proteins in Cancer and Intracellular Stress: A Therapeutic Perspective
Ong, M. S., Deng, S., Halim, C. E., Cai, W., Tan, T. Z., Huang, R. Y., Sethi, G., Hooi, S. C., Kumar, A. P., & Yap, C. T. (2020) · Cancers · doi:10.3390/cancers12010238 · Cited by 145
Endoplasmic reticulum stress in obesity and obesity-related disorders: An expanded view
Pagliassotti, M. J., Kim, P., Estrada, A. L., Stewart, C. M., & Gentile, C. L. (2016) · Metabolism · doi:10.1016/j.metabol.2016.05.002 · Cited by 137
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BackgroundImmunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy
Banik, D., Moufarrij, S., & Villagra, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092241 · Cited by 137
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Microtubule Dysfunction: A Common Feature of Neurodegenerative Diseases
Sferra, A., Nicita, F., & Bertini, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197354 · Cited by 138
“The same study showed that in vitro TSA treatments of rat cortical neurons expressing mutant LRKK2 increase tubulin acetylation and restore axonal transport [226].”
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Targeting Histone Deacetylases in Diseases: Where Are We?
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“HDAC6 and the enzyme functions as a tubulin deacetylase (98, 144, 257).”
BackgroundHistone Deacetylase 6 Regulates Human Immunodeficiency Virus Type 1 Infection
Valenzuela-Fernández, A., Álvarez, S., Gordón‐Alonso, M., Barrero-Villar, M., Ursa, Á., Cabrero, J. R., Fernández, G., Naranjo‐Suarez, S., Yáñez‐Mó, M., Serrador, J. M., et al. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-04-0354 · Cited by 126
“Histone deacetylase 6 (HDAC6) is exclusively located in the cytoplasm, and it regulates the acetylation of -tubulin (Hubbert et al., 2002; Matsuyama et al., 2002; Haggarty et al., 2003; Zhang et al., 2003).”
Functional Interaction between Class II Histone Deacetylases and ICP0 of Herpes Simplex Virus Type 1
Lomonte, P., Thomas, J., Texier, P., Caron, C., Khochbin, S., & Epstein, A. L. (2004) · Journal of Virology · doi:10.1128/jvi.78.13.6744-6757.2004 · Cited by 146
“Constructs expressing GST-HDAC4(1-650), -HDAC5,”
MethodInfluentialA novel GRK2/HDAC6 interaction modulates cell spreading and motility
Lafarga, V., Aymerich, I., Tapia, O., Mayor, F., & Penela, P. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.466 · Cited by 123
“…in the presence of GRK2-S670A or GRK2-K220R compared with wt protein (Supplementary Figure S2E) arguing against the possibility that such mutants could impair the potential bridging role of b -tubulin, with which GRK2 can interact (Pitcher et al , 1998), in such association (Zhang et al , 2003).”
Chemical regulation of epigenetic modifications: Opportunities for new cancer therapy
Zheng, Y. G., Wu, J., Chen, Z., & Goodman, M. (2008) · Medicinal Research Reviews · doi:10.1002/med.20120 · Cited by 126
Asthana, J., Kapoor, S., Mohan, R., & Panda, D. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.489328 · Cited by 123
“TSA has been used previously to elucidate the functions of HDAC6 (25, 27, 29) but has a disadvantage in that it is a general inhibitor of class I and II HDACs.”
MethodProtein Acetylation in Archaea, Bacteria, and Eukaryotes
Soppa, J. (2010) · Archaea · doi:10.1155/2010/820681 · Cited by 123
The Role of Ubiquitin in Autophagy-Dependent Protein Aggregate Processing
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“HDAC6 (class IIb) is the major tubulin deacetylase (Hubbert et al., 2002; Matsuyama et al., 2002; Zhang et al., 2003), whereas HDAC1, probably in the context of the NuRD complex, deacetylates p53 (Contreras et al.”
Deacetylation of Miro1 by HDAC6 blocks mitochondrial transport and mediates axon growth inhibition
Kalinski, A. L., Kar, A. N., Craver, J., Tosolini, A. P., Sleigh, J. N., Lee, S. J., Hawthorne, A. L., Brito‐Vargas, P., Miller-Randolph, S., Passino, R., et al. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201702187 · Cited by 119
“Acetylated K40 in α -tubulin is a substrate for HDAC6 (Hubbert et al., 2002; Matsuyama et al., 2002; Zhang et al., 2003).”
BackgroundWagner, F. F., Olson, D. E., Gale, J. P., Kaya, T., Weïwer, M., Aidoud, N., Thomas, M., Davoine, E. L., Lemercier, B. C., Zhang, Y., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301355j · Cited by 121
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Characterization of novel inhibitors of histone acetyltransferases
Eliseeva, E. D., Valkov, V., Jung, M., & Jung, M. O. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0159 · Cited by 121
“crotubule structures and may contribute to regulating microtubule dynamics (3).”
BackgroundLoss of Deacetylation Activity of Hdac6 Affects Emotional Behavior in Mice
Fukada, M., Hanai, A., Nakayama, A., Suzuki, T., Miyata, N., Rodriguiz, R. M., Wetsel, W. C., Yao, T., & Kawaguchi, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030924 · Cited by 122
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BackgroundTuning acetylation levels with HAT activators: Therapeutic strategy in neurodegenerative diseases
Selvi, B. R., Cassel, J., Kundu, T. K., & Boutillier, A. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2010.08.012 · Cited by 121
“In addition to histones, HATs and HDACs also use a number of nonhistone proteins as substrate [reviewed in 12] and change their biological functions via transcriptional-dependent and independent mechanisms [13,14].”
BackgroundTargeting HDAC6 attenuates nicotine-induced macrophage pyroptosis via NF-κB/NLRP3 pathway
Xu, S., Chen, H., Ni, H., & Dai, Q. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.11.021 · Cited by 117
Luminal Localization of α-tubulin K40 Acetylation by Cryo-EM Analysis of Fab-Labeled Microtubules
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“Regulation of the acetylation of a-tubulin by Ab and HDAC6 inhibitor It has been reported that Ab alters the level of acetylated atubulin in primary neuronal cultures and cell lines [10] whereas the HDAC6 inhibitor, TBA, promotes the acetylation of a-tubulin [19,20,21].”
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“Zhang et al. (2003) reported that HDAC6 interacts with purified tubulin and microtubules in vitro and that the inhibition of HDAC through TSA increases tubulin acetylation.55 Blagosklonny et al. (2002) showed that HDAC inhibitors differentially induce tubulin acetylation, mitotic arrest, and…”
BackgroundThe synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo
Chao, M., Lai, M.-J., Liou, J., Chang, Y., Wang, J.-C., Pan, S., & Teng, C. (2015) · Journal of Hematology & Oncology · doi:10.1186/s13045-015-0176-7 · Cited by 117
“HDAC6, which predominates in the cytoplasm [8], is responsible for tubulin deacetylation, which plays a key regulatory role in the stability of the dynamic microtubules [9–12].”
BackgroundSQSTM1/p62 Interacts with HDAC6 and Regulates Deacetylase Activity
Yan, J., Seibenhener, M. L., Calderilla‐Barbosa, L., Díaz-Meco, M. T., Moscat, J., Jiang, J., Wooten, M. W., & Wooten, M. C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076016 · Cited by 121
“Deacetylation of tubulin can be accomplished by the HDAC family of deacetylases [30,31].”
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Oncogenes induce a vimentin filament collapse mediated by HDAC6 that is linked to cell stiffness
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“HDAC6 activity increases the deacetylated form of microtubules (34, 35).”
BackgroundBobrowska, A., Paganetti, P., Matthias, P., & Bates, G. P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020696 · Cited by 112
“its main activity appears to be in the cytoplasm, where it has been shown to deacetylate a-tubulin, HSP90 and cortactin, among others [18,19,20,21].”
BackgroundPorter, N. J., Osko, J. D., Diedrich, D., Kurz, T., Hooker, J. M., Hansen, F. K., & Christianson, D. W. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01013 · Cited by 111
Roles and Targets of Class I and IIa Histone Deacetylases in Cardiac Hypertrophy
Kee, H. J., & Kook, H. Y. (2010) · BioMed Research International · doi:10.1155/2011/928326 · Cited by 114
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“including -tubulin (11, 12), cortactin (13), and HSP90 (14).”
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A Novel Class of Small Molecule Inhibitors of HDAC6
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“study revealed that HDAC6 promoted cell migration by deacetylated cytoplasmic proteins such as α-tubulin [45].”
BackgroundThe Role of HDAC6 in Autophagy and NLRP3 Inflammasome
Chang, P., Li, H., Hu, H., Li, Y., & Wang, T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.763831 · Cited by 103
Effects of cigarette smoke on pulmonary endothelial cells
Lü, Q., Gottlieb, E. R., & Rounds, S. (2018) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00373.2017 · Cited by 103
Histone deacetylase inhibitors – a new tool to treat cancer
Somech, R., Izraeli, S., & Simon, A. J. (2004) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2004.04.006 · Cited by 100
Histone Deacetylase Inhibitors in the Treatment of Hematological Malignancies and Solid Tumors
Federico, M., & Bagella, L. (2010) · BioMed Research International · doi:10.1155/2011/475641 · Cited by 103
“Here, we will discuss some of the recent developments in clinical trials utilizing HDACs inhibitors for the treatment of both hematological malignancies as well as solid tumors.”
Thaler, F., & Mercurio, C. (2013) · ChemMedChem · doi:10.1002/cmdc.201300413 · Cited by 99
N‐acetyltransferase ARD1‐NAT1 regulates neuronal dendritic development
Ohkawa, N., Sugisaki, S., Tokunaga, E., Fujitani, K., Hayasaka, T., Setou, M., & Inokuchi, K. (2008) · Genes to Cells · doi:10.1111/j.1365-2443.2008.01235.x · Cited by 96
The ATAC acetyl transferase complex controls mitotic progression by targeting non‐histone substrates
Orpinell, M., Fournier, M. L., Riss, A., Nagy, Z., Krebs, A. R., Frontini, M., & Tora, L. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.125 · Cited by 102
“To prove our hypothesis that SIRT2 is the major deacetylase involved in the observed phenotype, we aimed to exclude the potential contribution from the principal a-TDAC in the cells, HDAC6 (Hubbert et al, 2002; Zhang et al, 2003).”
BackgroundHDAC6 is required for invadopodia activity and invasion by breast tumor cells
Rey, M., Irondelle, M., Waharte, F., Lizárraga, F., & Chavrier, P. (2010) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2010.09.004 · Cited by 95
Biomarkers for predicting clinical responses to HDAC inhibitors
Stimson, L., & Thangue, N. B. L. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.03.016 · Cited by 96
“HDAC6, located in the cytoplasm where it acts as an atubulin deacetylase, may participate in regulating cell viability in response to mis-folded proteins [ 13 ].”
BackgroundTran, H., Nimick, M., Uhrig, R. G., Templeton, G. W., MORRICE, N. A., Gourlay, R., DeLong, A., & Moorhead, G. B. G. (2012) · The Plant Journal · doi:10.1111/j.1365-313x.2012.04984.x · Cited by 95
“proteins that are associated with taxol-stabilized microtubule polymers (Zhang et al., 2003).”
BackgroundTubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Katsetos, C. D., & Dráber, P. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212800626193 · Cited by 95
“A histone deacetylase class II enzyme (HDAC6), which is principally cytoplasmic [161], interacts with microtubules and deacetylates tubulin both on preassembled microtubules in vitro and in cells [162, 163].”
BackgroundCabrero, J. R., Serrador, J. M., Barreiro, O., Mittelbrunn, M., Naranjo-Suárez, S., Martín-Cófreces, N., Vicente-Manzanares, M., Mazitschek, R., Bradner, J. E., Ávila, J., et al. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-01-0008 · Cited by 95
“TSA is a broad HDACs inhibitor, whereas tubacin is specific for the tubulin deacetylase activity of HDAC6 (Hubbert et al., 2002; Matsuyama et al., 2002; Haggarty et al., 2003; Zhang et al., 2003).”
BackgroundStress granule: A promising target for cancer treatment
Gao, X., Jiang, L., Gong, Y., Chen, X., Ying, M., Zhu, H., He, Q., Yang, B., & Cao, J. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14790 · Cited by 98
“(2006) noted that HDAC6 could deacetylate tubulin and microtubule (Zhang et al., 2003), both of which are important SG components (Figure 4).”
BackgroundHDAC6: A unique HDAC family member as a cancer target
Kaur, S., Rajoria, P., & Chopra, M. (2022) · Cellular Oncology · doi:10.1007/s13402-022-00704-6 · Cited by 97
“Overexpression of HDAC6 leads to tubulin hypoacetylation and, hence, greater motility [39], whereas inhibition of HDAC6 leads to stabilization of microtubules.”
BackgroundRASSF1A, puppeteer of cellular homeostasis, fights tumorigenesis, and metastasis—an updated review
Dubois, F., Bergot, E., Zalcman, G., & Levallet, G. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2169-x · Cited by 95
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“Several HDAC inhibitors are in clinical development where activity has been observed mainly in haematological malignancies.”
BackgroundInfluentialVorinostat increases carboplatin and paclitaxel activity in non‐small cell lung cancer cells
Owonikoko, T. K., Ramalingam, S. S., Kanterewicz, B. I., Balius, T. E., Belani, C. P., & Hershberger, P. A. (2009) · International Journal of Cancer · doi:10.1002/ijc.24759 · Cited by 90
“Pharmacological inhibition of HDAC6 activity in cultured cells leads to an increase in tubulin acetylation and microtubule stabilization.(18) Because paclitaxel binds preferentially to polymerized tubulin,(19) vorinostat, by inhibiting HDAC6, may decrease the concentration of”
BackgroundHu, T., Gibson, D. P., Carr, G. J., Torontali, S. M., Tiesman, J. P., Chaney, J. G., & Aardema, M. J. (2004) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.11.012 · Cited by 88
Drug Insight: histone deacetylase inhibitor-based therapies for cutaneous T-cell lymphomas
Khan, O. A., & Thangue, N. B. L. (2008) · Nature Clinical Practice Oncology · doi:10.1038/ncponc1238 · Cited by 88
“HDAC6, for example, is located in the cytoplasm, where it acts as an α-tubulin deacetylas”
BackgroundPatil, V., Guerrant, W., Chen, P. C., Gryder, B. E., Benicewicz, D. B., Khan, S. I., Tekwani, B. L., & Oyelere, A. K. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.10.042 · Cited by 86
The Relative Densities of Cytoplasm and Nuclear Compartments Are Robust against Strong Perturbation
Kim, K., & Guck, J. R. (2020) · Biophysical Journal · doi:10.1016/j.bpj.2020.08.044 · Cited by 85
Effects of Histone Deacetylase Inhibitors on HIF-1
Liang, D., Kong, X., & Sang, N. (2006) · Cell Cycle · doi:10.4161/cc.5.21.3409 · Cited by 85
The therapeutic hope for HDAC6 inhibitors in malignancy and chronic disease
Batchu, S. N., Brijmohan, A. S., & Advani, A. (2016) · Clinical Science · doi:10.1042/cs20160084 · Cited by 86
Histone modification enzymes: novel targets for cancer drugs
Kristeleit, R. S., Stimson, L., Workman, P., & Aherne, W. (2004) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.9.1.135 · Cited by 86
“These enzymes determine the acetylation state, not just of histones but also of other substrates, such as p53 [31-36].”
BackgroundStrategies in developing promising histone deacetylase inhibitors
Zhang, L., Fang, H., & Xu, W. (2009) · Medicinal Research Reviews · doi:10.1002/med.20169 · Cited by 83
The Therapeutic Strategy of HDAC6 Inhibitors in Lymphoproliferative Disease
Cosenza, M., & Pozzi, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082337 · Cited by 84
“It is mainly localized in the cytoplasm and has been described as a tubulin deacetylase that has effects on microtubule-mediated processes through both deacetylase-dependent and independent mechanisms [33,34].”
BackgroundCatalano, M. G., Poli, R., Pugliese, M., Fortunati, N., & Boccuzzi, G. (2007) · Endocrine Related Cancer · doi:10.1677/erc-07-0096 · Cited by 84
“Zhang et al. (2003) reported that HDAC6 is a microtubule-associated protein capable of deacetylating a -tubulin in vitro and in vivo , and that HDI treatment leads to hyperacetylation of tubulin and microtubules.”
BackgroundInfluentialAlcohol-induced protein hyperacetylation: Mechanisms and consequences
Shepard, B. D. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.1219 · Cited by 83
Medicinal chemistry updates of novel HDACs inhibitors (2020 to present)
He, X., Hui, Z., Xu, L., Bai, R., Gao, Y., Wang, Z., Xie, T., & Ye, X.-Y. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113946 · Cited by 89
Morris, M. J., Karra, A. S., & Monteggia, L. M. (2010) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32833c20c0 · Cited by 83
“HDAC6 KO mice are an exception – they are viable and have no discernible phenotype beyond hyperacetylated tubulin (Hubbert et al., 2002; Zhang et al., 2003).”
BackgroundHuman histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules
Skultetyova, L., Ustinova, K., Kutil, Z., Nováková, Z., Pavlı́ček, J., Mikesova, J., Trapl, D., Baranová, P., Havlínová, B., Hubálek, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11739-3 · Cited by 82
Osko, J. D., & Christianson, D. W. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00934 · Cited by 81
Nahhas, F. A., Dryden, S. C., Abrams, J., & Tainsky, M. A. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9478-6 · Cited by 81
“This is not surprising as btubulin binds to the HDAC6 catalytic domain when associated with PP1 [43, 44].”
BackgroundInfluentialBorgas, D. L., Chambers, E., Newton, J., Ko, J., Rivera, S. E., Rounds, S., & Lü, Q. (2015) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2015-0149oc · Cited by 80
Role of histone deacetylases and their inhibitors in neurological diseases
Zhang, L.-Y., Zhang, S.-Y., Wen, R., Zhang, T.-N., & Yang, N. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107410 · Cited by 84
Histone Deacetylase Inhibitors as Therapeutic Agents for Acute Central Nervous System Injuries
Shein, N. A., & Shohami, E. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00038 · Cited by 79
Giustiniani, J., Daire, V., Cantaloube, I., Durand, G., Poüs, C., Perdiz, D., & Baillet, A. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.12.004 · Cited by 80
Chapter 4 Ciliary Tubulin and Its Post-Translational Modifications
Gaertig, J., & Włoga, D. (2008) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(08)00804-1 · Cited by 79
Noack, M., Leyk, J., & Richter‐Landsberg, C. (2014) · Glia · doi:10.1002/glia.22624 · Cited by 77
“…dependent on the second catalytic domain of HDAC6 which is affected by specific inhibitors such as tubacin and tubastatin A (Haggarty et al., 2003; Zhang et al., 2003; Zilberman et al., 2009). a2Tubulin acetylation, occurring on polymerized MTs, has been connected to an increase in stability, but…”
BackgroundSubstrate and inhibitor specificity of class 1 and class 2 histone deacetylases
Hildmann, C., Wegener, D., Riester, D., Hempel, R., Schober, A., Merana, J., Giurato, L., Guccione, S., Nielsen, T. K., Ficner, R., et al. (2006) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2006.01.030 · Cited by 78
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“A-tubulin is a endogenous substrate of HDAC6 [46,80], acetylation of the α-tubulin at Lys40 stabilizes microtubule structure [46, 81] and overexpression of HDAC6 specifically reduces the acetylation levels of α-tubulin [48].”
BackgroundCorepressor Recruitment by Agonist-Bound Nuclear Receptors
White, J. H., Fernandes, I., Mader, S., & Yang, X. (2004) · Vitamins and hormones · doi:10.1016/s0083-6729(04)68004-6 · Cited by 85
Koeneke, E., Witt, O., & Oehme, I. (2015) · Cells · doi:10.3390/cells4020135 · Cited by 76
“Class IIb HDACs seem to have primarily cytoplasmic roles, with HDAC6 deacetylating alpha-tubulin and functioning as part of protein aggresome formation and processing [84–86].”
BackgroundThe emerging role of lysine acetylation of non-nuclear proteins
Close, P., Creppe, C., Gillard, M., Ladang, A., Chapelle, J.-P., Nguyen, L., & Chariot, A. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0252-7 · Cited by 79
“peroxiredoxins in this cell compartment [10–15].”
BackgroundYan, J. (2014) · DNA and Cell Biology · doi:10.1089/dna.2013.2300 · Cited by 77
“These include cytoplasmic substrates of HDAC6, such as a -tubulin, cortactin, and heat shock protein 90 (Hsp90) (Zhang et al. , 2003, 2007; Kovacs et al. , 2005).”
Microtubule Acetylation Through HDAC6 Inhibition Results in Increased Transfection Efficiency
Vaughan, E. E., Geiger, R., Miller, A. M., Loh-Marley, P. L., Suzuki, T., Miyata, N., & Dean, D. A. (2008) · Molecular Therapy · doi:10.1038/mt.2008.190 · Cited by 77
Wienecke-Baldacchino, A. K., & Bacher, G. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1342 · Cited by 76
“The only acetylation site of a-tubulin, Lys40, is acetylated (35), and it is possible that modification of this amino acid might prevent indibulin from accessing its binding site.”
BackgroundLi, X., Inks, E. S., Li, X., Hou, J., Chou, C. J., Zhang, J., Jiang, Y., Zhang, Y., & Xu, W. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401877m · Cited by 76
Microtubule associated proteins as targets for anticancer drug development
Khwaja, S., Kumar, K., Das, R., & Negi, A. S. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105320 · Cited by 76
The role of altered protein acetylation in neurodegenerative disease
Kabir, F., Atkinson, R., Cook, A. L., Phipps, A. J., & King, A. E. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1025473 · Cited by 75
HDAC6 and SIRT2 promote bladder cancer cell migration and invasion by targeting cortactin
Chen, W. (2011) · Oncology Reports · doi:10.3892/or.2011.1553 · Cited by 75
“In one previous study, both HDAC6 catalytic domains were required for full tubulin deacetylase (TDAC) activity (19,20); however, in other studies the TDAC activity was attributed to the second domain (16,21,22).”
Impact of protein acetylation in inflammatory lung diseases
Ito, K., Charron, C. E., & Adcock, I. M. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.06.009 · Cited by 77
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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