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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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Acetylation and deacetylation of non-histone proteins
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BackgroundFunctions and mechanisms of non-histone protein acetylation
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“HDAC6 has been shown to function as an α-tubulin deacetylas”
Background
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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