PMID:12606581

Citation	Zhang, Y, Li, N, Caron, C, Matthias, G, Hess, D, Khochbin, S and Matthias, P (2003) HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J. 22:1168-79
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.
Links	PubMed PMC150348 Online version:10.1093/emboj/cdg115
Keywords	3T3 Cells; Acetylation; Animals; Cattle; Chromatography, High Pressure Liquid; Embryo, Mammalian/anatomy & histology; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Humans; Kidney/cytology; Mice; Microtubules/metabolism; Paclitaxel/metabolism; Peptides/chemistry; Peptides/metabolism; Protein Binding; Protein Structure, Tertiary; Stem Cells/cytology; Stem Cells/metabolism; Tubulin/chemistry; Tubulin/metabolism; Two-Hybrid System Techniques
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:HDAC6	part_of	GO:0015630: microtubule cytoskeleton	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:HDAC6	colocalizes_with	GO:0005881: cytoplasmic microtubule	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:HDAC6	enables	GO:0042903: tubulin deacetylase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:HDAC6	enables	GO:0048487: beta-tubulin binding	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:HDAC6	acts_upstream_of_or_within	GO:0090042: tubulin deacetylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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