Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition
Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition
复制标题
α-微管蛋白乙酰化的丧失与 TGF-β 诱导的上皮间质转化有关。
DOI：
10.1074/jbc.m115.713123
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发表时间：
2016-03-04
影响因子：
4.8
通讯作者：
Feng, Xin-Hua
中科院分区：
文献类型：
--
作者：
Gu, Shuchen;Liu, Yanjing;Feng, Xin-Hua
上皮-间充质转化（EMT）是分化的上皮细胞重新编程基因表达、失去其连接和极性、重组其细胞骨架、增加细胞运动性并呈现间充质形态的过程。尽管微管（MT）在细胞骨架组织中的关键功能，但它如何参与EMT的诱导和维持仍然知之甚少。在这里，我们报告乙酰化微管蛋白，这在微管（MT）的稳定和细胞形态中起着重要的作用，可以作为一个新的调节剂和EMT的标志物。高水平的乙酰化微管蛋白与上皮细胞形态学相关，在TGF-β诱导的EMT过程中，乙酰化微管蛋白水平显著降低.我们发现，TGF-β 1增加HDAC6，微管蛋白的主要脱乙酰酶的活性，而不影响其表达水平。用HDAC 6抑制剂微管蛋白或TGF-1型受体抑制剂SB 431542治疗恢复了乙酰化微管蛋白的水平，从而阻断了EMT。我们的研究结果表明，乙酰化微管蛋白可以作为EMT的标志物，HDAC 6是EMT过程中的重要调节因子。
The epithelial-to-mesenchymal transition (EMT) is a process by which differentiated epithelial cells reprogram gene expression, lose their junctions and polarity, reorganize their cytoskeleton, increase cell motility and assume a mesenchymal morphology. Despite the critical functions of the microtubule (MT) in cytoskeletal organization, how it participates in EMT induction and maintenance remains poorly understood. Here we report that acetylated -tubulin, which plays an important role in microtubule (MT) stabilization and cell morphology, can serve as a novel regulator and marker of EMT. A high level of acetylated -tubulin was correlated with epithelial morphology and it profoundly decreased during TGF--induced EMT. We found that TGF- increased the activity of HDAC6, a major deacetylase of -tubulin, without affecting its expression levels. Treatment with HDAC6 inhibitor tubacin or TGF- type I receptor inhibitor SB431542 restored the level of acetylated -tubulin and consequently blocked EMT. Our results demonstrate that acetylated -tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process.