Cited by 741Histone Deacetylase Inhibitors ResearchMicrotubule and mitosis dynamicsGenomics and Chromatin Dynamics

In vivo destabilization of dynamic microtubules by HDAC6‐mediated deacetylation

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Matsuyama, Akihisa, Shimazu, Tadahiro, Sumida, Yuko, Saito, Akiko, Yoshimatsu, Yasuhiro, Seigneurin‐Berny, Daphné, Osada, Hiroyuki, Komatsu, Yasuhiko +4 more·2002·The EMBO Journal

Abstract

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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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
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
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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