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In vivo destabilization of dynamic microtubules by HDAC6‐mediated deacetylation
Author(s) -
Matsuyama Akihisa,
Shimazu Tadahiro,
Sumida Yuko,
Saito Akiko,
Yoshimatsu Yasuhiro,
SeigneurinBerny Daphné,
Osada Hiroyuki,
Komatsu Yasuhiko,
Nishino Norikazu,
Khochbin Saadi,
Horinouchi Sueharu,
Yoshida Minoru
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf682
Subject(s) - acetylation , hdac6 , microtubule , tubulin , trichostatin a , in vivo , microbiology and biotechnology , chemistry , histone , depolymerization , cytoplasm , biochemistry , biophysics , histone deacetylase , biology , genetics , organic chemistry , gene
Trichostatin A (TSA) inhibits all histone deacetylases (HDACs) of both class I and II, whereas trapoxin (TPX) cannot inhibit HDAC6, a cytoplasmic member of class II HDACs. We took advantage of this differential sensitivity of HDAC6 to TSA and TPX to identify its substrates. Using this approach, α‐tubulin was identified as an HDAC6 substrate. HDAC6 deacetylated α‐tubulin both in vivo and in vitro . Our investigations suggest that HDAC6 controls the stability of a dynamic pool of microtubules. Indeed, we found that highly acetylated microtubules observed after TSA treatment exhibited delayed drug‐induced depolymerization and that HDAC6 overexpression prompted their induced depolymerization. Depolymerized tubulin was rapidly deacetylated in vivo , whereas tubulin acetylation occurred only after polymerization. We therefore suggest that acetylation and deacetylation are coupled to the microtubule turnover and that HDAC6 plays a key regulatory role in the stability of the dynamic microtubules.