A New Chromatin-Cytoskeleton Link in Cancer.
A New Chromatin-Cytoskeleton Link in Cancer.
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DOI：
10.1158/1541-7786.mcr-16-0250
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发表时间：
2016-12
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影响因子：
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通讯作者：
Giaccia AJ
中科院分区：
文献类型：
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作者：
Giaccia AJ
SET结构域包含2(SETD2)组蛋白甲基转移酶，位于3p2，特异三甲基化组蛋白H3(H3K36me3)的赖氨酸36。H3K36me3是参与转录延伸和RNA加工的活性标记，也是DNA修复的关键调控因子。事实上，SETD2是唯一一种“写”H3K36me3标记的甲基转移酶。Park等人最近的结果发现，SETD2在α-微管蛋白K40的甲基化中起到了新的作用。α-微管蛋白K40甲基化缺失，导致有丝分裂纺锤体功能障碍和胞质分裂异常。因此，SETD2通过其甲基转移酶活性将染色质和细胞骨架的动态平衡联系起来。这些研究对SETD2突变在促进基因组不稳定和肿瘤进展中的作用具有重要意义。
The set domain containing 2 (SETD2) histone methyltransferase, located at 3p2, specifically trimethylates lysine 36 of histone H3 (H3K36me3). H3K36me3 is an active mark involved in transcriptional elongation and RNA processing, and a key regulator of DNA repair. In fact, SETD2 is the only methyltransferase that “writes” the H3K36me3 mark. Recent results from Park et al have found a new role for SETD2 in the methylation of K40 of α-tubulin. Loss of SETD2 abolishes methylation of K40 of α-tubulin, and results in a dysfunctional mitotic spindle and abnormalities in cytokinesis. Thus, SETD2 links chromatin and cytoskeleton homeostasis through its methyltransferase activity. These studies have important implications on the role of SETD2 mutations in promoting genomic instability and tumor progression.