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

• Published in: The EMBO journal Vol. 22; no. 5; pp. 1168 - 1179
• Main Authors: Zhang, Yu, Li, Na, Caron, Cécile, Matthias, Gabriele, Hess, Daniel, Khochbin, Saadi, Matthias, Patrick
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 03.03.2003; Blackwell Publishing Ltd; Oxford University Press
• Subjects: 3T3 Cells; Acetylation; Animals; Cattle; chromatin; Chromatography, High Pressure Liquid; cytoskeleton; deacetylase; Embryo, Mammalian - anatomy & histology; HDAC (histone deacetylase); Histone Deacetylase 6; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Humans; Inactivation; Inhibitors; Kidney - cytology; Mice; Microtubules - metabolism; Paclitaxel - metabolism; Peptides - chemistry; Peptides - metabolism; Protein Binding; Protein Structure, Tertiary; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; tubulin; Tubulin - chemistry; Tubulin - metabolism; Two-Hybrid System Techniques; Yeasts
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1093/emboj/cdg115

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 ϵ‐amino group of α‐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 β‐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 α‐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.