Acetylated tubulin is associated with stable microtubule structures. Hubbert et al. identified a member of the histone deacetylase (HDAC) family HDAC6 as a deacetylase that colocalized with microtubules in cells. Overexpression of HDAC6 in NIH 3T3 cells promoted deacetylation of α-tubulin. In cells in which HDAC6 was inhibited with either pharmacological manipulation or short interfering RNAs (to inhibit expression of the protein), acetylated tubulin was more abundant than in untreated cells. In vitro, HDAC6 deacetylated polymerized microtubule but did not exhibit activity toward free α-β tubulin dimers. Functionally, HDAC6 activity may regulate microtubule stability involved in cell movement, because HDAC6 overexpression promoted more rapid movement in response to chemotactic stimuli than that observed for control cells.
C. Hubbert, A. Guardiola, R. Shao, Y. Kawaguchi, A. Ito, A. Nixon, M. Yoshida, X.-F. Want, T.-P. Yao, HDAC6 is a microtubule-associated deactylase. Nature 417, 455-458 (2002). [Online Journal]