HDAC6 is a microtubule-associated deacetylase
HDAC6 is a microtubule-associated deacetylase
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DOI：
10.1038/417455a
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发表时间：
2002-05-23
期刊：
影响因子：
64.8
通讯作者：
Yao, TP
中科院分区：
文献类型：
--
作者：
Hubbert, C;Guardiola, A;Yao, TP
α-微管蛋白的可逆乙酰化与调节微管稳定性和功能有关（1）。乙酰化α-微管蛋白的分布是严格控制和定型的。乙酰化α-微管蛋白在稳定的微管中含量最高，但在动态细胞结构如神经元生长锥和成纤维细胞的前缘中不存在（1，2）。然而，负责调节微管蛋白乙酰化和去乙酰化的酶是未知的。在这里，我们报告的组蛋白去乙酰化酶家族的成员，HDAC 6，作为微管蛋白去乙酰化酶的功能。HDAC 6仅定位于细胞质中，在那里它与微管结合，并定位于含有p150的微管运动复合体（胶合）（参考文献3）。在体内，HDAC 6的过表达导致α-微管蛋白的整体脱乙酰化，而HDAC 6的减少增加α-微管蛋白乙酰化。在体外，纯化的HDAC 6有效地使组装的微管中的α-微管蛋白脱乙酰基。此外，HDAC 6的过表达促进趋化细胞运动，支持HDAC 6介导的去乙酰化调节微管依赖性细胞运动的观点。我们的研究结果表明，HDAC 6是微管蛋白脱乙酰酶，并提供证据，可逆乙酰化调节重要的生物过程以外的组蛋白代谢和基因转录。
Reversible acetylation of alpha-tubulin has been implicated in regulating microtubule stability and function(1). The distribution of acetylated alpha-tubulin is tightly controlled and stereotypic. Acetylated alpha-tubulin is most abundant in stable microtubules but is absent from dynamic cellular structures such as neuronal growth cones and the leading edges of fibroblasts(1,2). However, the enzymes responsible for regulating tubulin acetylation and deacetylation are not known. Here we report that a member of the histone deacetylase family, HDAC6, functions as a tubulin deacetylase. HDAC6 is localized exclusively in the cytoplasm, where it associates with microtubules and localizes with the microtubule motor complex containing p150(glued) (ref. 3). In vivo, the overexpression of HDAC6 leads to a global deacetylation of alpha-tubulin, whereas a decrease in HDAC6 increases alpha-tubulin acetylation. In vitro, purified HDAC6 potently deacetylates alpha-tubulin in assembled microtubules. Furthermore, overexpression of HDAC6 promotes chemotactic cell movement, supporting the idea that HDAC6-mediated deacetylation regulates microtubule-dependent cell motility. Our results show that HDAC6 is the tubulin deacetylase, and provide evidence that reversible acetylation regulates important biological processes beyond histone metabolism and gene transcription.