title: Histone deacetylase 3 indirectly modulates tubulin acetylation.
abstract: Histone deacetylase 3 (HDAC3), a member of the Class I subfamily of HDACs, is found in both the nucleus and the cytoplasm. Its roles in the nucleus have been well characterized, but its cytoplasmic roles are still not elucidated fully. We found that blocking HDAC3 activity using MI192, a compound specific for HDAC3, modulated tubulin acetylation in the human prostate cancer cell line PC3. A brief 1 h treatment of PC3 cells with MI192 significantly increased levels of tubulin acetylation and ablated the dynamic behaviour of microtubules in live cells. siRNA-mediated knockdown (KD) of HDAC3 in PC3 cells, significantly increased levels of tubulin acetylation, and overexpression reduced it. However, the active HDAC3-silencing mediator of retinoic and thyroid receptors (SMRT)-deacetylase-activating domain (DAD) complex did not directly deacetylate tubulin in vitro. These data suggest that HDAC3 indirectly modulates tubulin acetylation.
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Travis
authors.initials: T
authors.lastname: Bacon
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Caroline
authors.initials: C
authors.lastname: Seiler
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wolny
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Department of Molecular and Cell Biology, Henry Wellcome Laboratories of Structural Biology, University of Leicester, Lancaster Road, Leicester LE1 9HN, U.K.
authors.forename: Peter
authors.initials: P
authors.lastname: Watson
authors.affiliation: Department of Molecular and Cell Biology, Henry Wellcome Laboratories of Structural Biology, University of Leicester, Lancaster Road, Leicester LE1 9HN, U.K.
authors.forename: John
authors.initials: J
authors.lastname: Schwabe
authors.affiliation: School of Chemistry, Faculty of Maths and Physical Sciences, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Ronald
authors.initials: R
authors.lastname: Grigg
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K. m.peckham@leeds.ac.uk.
authors.forename: Michelle
authors.initials: M
authors.lastname: Peckham
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D056985:Nuclear Receptor Co-Repressor 2 / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D001549:Benzamides; D006655:Histone Deacetylases; D056985:Nuclear Receptor Co-Repressor 2; D014404:Tubulin; D000099186:Histone Deacetylase 3; C576022:MI-192; C539130:NCOR2 protein, human
keywords: acetylation; histone deacetylase 3; microtubules; tubulin