New HDAC6-mediated deacetylation sites of tubulin in the mouse brain identified by quantitative mass spectrometry.
New HDAC6-mediated deacetylation sites of tubulin in the mouse brain identified by quantitative mass spectrometry.
复制标题
通过定量质谱法鉴定小鼠大脑中新的 HDAC6 介导的微管蛋白脱乙酰位点
DOI：
10.1038/srep16869
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发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
Shui W
中科院分区：
文献类型：
--
作者：
Liu N;Xiong Y;Li S;Ren Y;He Q;Gao S;Zhou J;Shui W
发生在微管上的翻译后修饰（PTMs）参与了微管性质和功能的调控。α-微管蛋白的乙酰化K40是长寿命稳定微管的标志，已知由组蛋白去乙酰化酶6 （HDAC6）负调控。然而，HDAC6在微管相关过程中的重要作用，如细胞运动和细胞分裂，并不能完全由微管蛋白上唯一已知的靶点来解释。在这里，我们试图全面绘制从小鼠脑组织中纯化的微管蛋白上的赖氨酸乙酰化位点。此外，基于质谱的定量比较野生型和HDAC6基因敲除小鼠的乙酰化肽使我们确定了六个可能由HDAC6介导的新去乙酰化位点。因此，在HDAC6介导的微管蛋白去乙酰化事件中增加新的位点将进一步加深我们对HDAC6在调节微管稳定性和细胞功能方面的多方面作用的理解。
The post-translational modifications (PTMs) occurring on microtubules have been implicated in the regulation of microtubule properties and functions. Acetylated K40 of α-tubulin, a hallmark of long-lived stable microtubules, is known to be negatively controlled by histone deacetylase 6 (HDAC6). However, the vital roles of HDAC6 in microtubule-related processes such as cell motility and cell division cannot be fully explained by the only known target site on tubulin. Here, we attempt to comprehensively map lysine acetylation sites on tubulin purified from mouse brain tissues. Furthermore, mass spectrometry-based quantitative comparison of acetylated peptides from wild-type vs HDAC6 knockout mice allowed us to identify six new deacetylation sites possibly mediated by HDAC6. Thus, adding new sites to the repertoire of HDAC6-mediated tubulin deacetylation events would further our understanding of the multi-faceted roles of HDAC6 in regulating microtubule stability and cellular functions.