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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]
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“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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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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