The DOI matches its Crossref record; 43 of the 45 references it cites were found in a registry or an index.
In vivo destabilization of dynamic microtubules by HDAC6‐mediated deacetylation
Open accessAbstract
Trichostatin A (TSA) inhibits all histone deacetylases (HDACs) of both class I and II, whereas trapoxin (TPX) cannot inhibit HDAC6, a cytoplasmic member of class II HDACs. We took advantage of this differential sensitivity of HDAC6 to TSA and TPX to identify its substrates. Using this approach, alpha-tubulin was identified as an HDAC6 substrate. HDAC6 deacetylated alpha-tubulin both in vivo and in vitro. Our investigations suggest that HDAC6 controls the stability of a dynamic pool of microtubules. Indeed, we found that highly acetylated microtubules observed after TSA treatment exhibited delayed drug-induced depolymerization and that HDAC6 overexpression prompted their induced depolymerization. Depolymerized tubulin was rapidly deacetylated in vivo, whereas tubulin acetylation occurred only after polymerization. We therefore suggest that acetylation and deacetylation are coupled to the microtubule turnover and that HDAC6 plays a key regulatory role in the stability of the dynamic microtubules.
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“HDAC6, a tubulin deacetylase [24].”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [31]
In the citing paper
“Acelylation of α-tubulin, which promotes microtubule stabilisation, may distort mitosis and trigger apoptosis (Matsuyama et al, 2002); it can also affect changes in cell motility and, hence, invasion and metastasis of cancer cells (Hubbert et al, 2002).”
From A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth (2013) · cites this paper as Matsuyama et al, 2002
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Pharmacological Inhibition of HDAC6 Transiently Reduces Voluntary Ethanol Consumption in Male Mice
Fleck, K., Dunning, J. L., Kreifeldt, M., Lopez, C., Jo, S., Roberts, E., & Contet, C. (2026) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.70380
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Ren, H., Nie, J., Song, Z., Mo, W., Yang, Y., & Bai, Z. (2026) · Biotechnology Journal · doi:10.1002/biot.70313
Cao, Y., Chen, J., & Chu, X. (2026) · eLife · doi:10.7554/elife.112787
Cao, Y., Chen, J., & Chu, X. (2026) · eLife · doi:10.7554/elife.112787.1
BindingDB Entry 50011516: Recent advances in the discovery of potent and selective HDAC6 inhibitors.
BindingDB (2022) · UC San Diego · doi:10.7270/q25h7kv7
BindingDB (2020) · UC San Diego · doi:10.7270/q27s7rjn
BindingDB (2016) · UC San Diego · doi:10.7270/q2v986v6
BindingDB Entry 50020079: Design and synthesis of a potent histone deacetylase inhibitor.
BindingDB (2009) · UC San Diego · doi:10.7270/q26m36h1
BindingDB Entry 50033616: A novel HDAC inhibitor with a hydroxy-pyrimidine scaffold.
BindingDB (2012) · UC San Diego · doi:10.7270/q20p10ct
BindingDB Entry 50033283: Discovery of histone deacetylase 8 selective inhibitors.
BindingDB (2011) · UC San Diego · doi:10.7270/q2zc835m
BindingDB Entry 50037213: Histone deacetylase inhibitors.
BindingDB (2012) · UC San Diego · doi:10.7270/q2mp5413
Mechanisms Underlying the Heterogeneous Sensitivities of Cancer Cells to Proteasome Inhibitors
White, M. C. (2013) · Digital Commons-TMC (Texas Medical Center)
Die Wirkung von Valproat auf die Konochenmetastasenzellen (VCaP) des Prostatakarzinoms
Früchtenicht, T. (2011) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-1070
Metadata
- Authors
- Matsuyama, A., Shimazu, T., Sumida, Y., Saito, A., Yoshimatsu, Y., Seigneurin‐Berny, D., Osada, H., Komatsu, Y., Nishino, N., Khochbin, S., Horinouchi, S., & Yoshida, M.
- Affiliations
- RIKEN (JP)
- The University of Tokyo (JP)
- Inserm (FR)
- Kyushu Institute of Technology (JP)
- Corresponding author
- Yoshida, Minoru
- Venue
- The EMBO Journal
- Published
- 2002-12-16
- Volume
- 21
- Issue
- 24
- Pages
- 6820-6831
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC139102
- OpenAlex
- W2148495272
- Cited by
- 720
- References
- 45
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 14 · 2023: 27 · 2022: 15 · 2021: 28 · 2020: 25 · 2019: 29 · 2018: 27 · 2017: 33 · 2016: 35 · 2015: 36 · 2014: 34 · 2013: 45 · 2012: 45
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Corporation (CREST)
- Core Research for Evolutional Science and Technology
- 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
- HDAC6, histone deacetylase, alpha-tubulin, tubulin acetylation, microtubule stability, microtubule dynamics, microtubule depolymerization, trichostatin A, class II HDACs, tubulin deacetylation, microtubule turnover
- MeSH terms
- Histone Deacetylase 6, Acetylation, Ethanol, Animals, Antineoplastic Agents, Phytogenic, Demecolcine, Histone Deacetylases, Microscopy, Fluorescence, Microtubules, Peptides, Plasmids, Precipitin Tests, Protein Binding, Time Factors, Transfection, Tubulin, Immunoblotting, NIH 3T3 Cells, Mice
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