HDAC6介导的去乙酰化作用对动态微管进行体内失稳处理。
In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation.
作者信息
Matsuyama Akihisa, Shimazu Tadahiro, Sumida Yuko, Saito Akiko, Yoshimatsu Yasuhiro, Seigneurin-Berny Daphné, Osada Hiroyuki, Komatsu Yasuhiko, Nishino Norikazu, Khochbin Saadi, Horinouchi Sueharu, Yoshida Minoru
机构信息
Chemical Genetics Laboratory, Wako, Saitama 351-0198, Japan.
出版信息
EMBO J. 2002 Dec 16;21(24):6820-31. doi: 10.1093/emboj/cdf682.
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, alpha-tubulin was identified as an HDAC6 substrate. HDAC6 deacetylated alpha-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.
曲古抑菌素A（TSA）可抑制I类和II类所有组蛋白去乙酰化酶（HDAC），而 Trapoxin（TPX）不能抑制II类HDAC的胞质成员HDAC6。我们利用HDAC6对TSA和TPX的这种差异敏感性来鉴定其底物。通过这种方法，α-微管蛋白被鉴定为HDAC6的底物。HDAC6在体内和体外均使α-微管蛋白去乙酰化。我们的研究表明，HDAC6控制着动态微管池的稳定性。事实上，我们发现TSA处理后观察到的高度乙酰化微管表现出药物诱导的解聚延迟，而HDAC6的过表达促使它们发生诱导解聚。解聚的微管蛋白在体内迅速去乙酰化，而微管蛋白乙酰化仅在聚合后发生。因此，我们认为乙酰化和去乙酰化与微管周转相关，并且HDAC6在动态微管的稳定性中起关键调节作用。
Zotero 插件