Cited by 766Histone Deacetylase Inhibitors ResearchMicrotubule and mitosis dynamicsGenomics and Chromatin Dynamics

HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo

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Zhang, Yu, Li, Na, Caron, Cécile, Matthias, Gabriele, Hess, Daniel, Khochbin, Saadi, Matthias, Patrick·2003·The EMBO Journal

Abstract

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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  • HDAC6 has been associated with deacetylation of several cytosolic substrates including α-tubulin and p53.

    “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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  1. Richon,V.M., Sandhoff,T.W., Rifkind,R.A. and Marks,P.A. (2000) Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc. Natl Acad. Sci. USA, 97, 10014±10019.

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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
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
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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