SIRT2 inactivation reveals a subset of hyperacetylated perinuclear microtubules inaccessible to HDAC6.
Deacetylation of α-tubulin at lysine 40 is catalyzed by two enzymes, the NAD-dependent deacetylase SIRT2 and the NAD-independent deacetylase HDAC6, in apparently redundant reactions. In the present study, we tested whether these two enzymes might have distinguishable preferences for the deacetylation of different microtubule structures. Using various agents, we induced tubulin hyperacetylation and analyzed the ensuing formation of distinct microtubule structures. HDAC6 inhibition led to general hyperacetylation of the microtubule network throughout the cell, whereas hyperacetylation induced by SIRT2 inactivation was limited to perinuclear microtubules. Hyperacetylation of these perinuclear microtubules was undiminished following HDAC6 overexpression, whereas reactivation of SIRT2 restored the basal acetylation level and a normal microtubule network. By contrast, SIRT2 and HDAC6 acted similarly on the morphologically different, hyperacetylated microtubule structures induced by taxol, MAP2c overexpression or hyperosmotic stress. These results indicate overlapping and distinct functions of HDAC6 and SIRT2. We propose that the differential activity of the two deacetylases, which target the same acetylated lysine residue, might be related to the recognition of specific structural contexts.
Department of Molecular Biology, University of Bergen, Postbox 7803, Bergen 5020, Norway.
Renate Hvidsten
RH
Skoge
Department of Molecular Biology, University of Bergen, Postbox 7803, Bergen 5020, Norway mathias.ziegler@uib.no.
Mathias
0000-0001-6961-2396
M
Ziegler
D000107:Acetylation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003080:Cold Temperature; D006367:HeLa Cells; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D056565:Sirtuin 2 / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D014404:Tubulin; D056565:Sirtuin 2; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D017239:Paclitaxel
HDAC6; Microtubules; SIRT2; Tubulin deacetylation