Identification and functional implication of nuclear localization signals in the N-terminal domain of JMJD5
Identification and functional implication of nuclear localization signals in the N-terminal domain of JMJD5
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JMJD5 N端结构域核定位信号的鉴定及其功能意义
DOI：
10.1016/j.biochi.2013.08.002
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发表时间：
2013-11-01
期刊：
影响因子：
3.9
通讯作者：
Shen, Jing
中科院分区：
文献类型：
--
作者：
Huang, Xiaobin;Zhang, Lingna;Shen, Jing
JMJD 5最近被报道参与昼夜节律调节、胚胎发育、破骨细胞生成和肿瘤发生。虽然JMJD5主要定位于细胞核中，但它如何进入细胞核仍不清楚。在这里，我们报告说，JMJD 5包含一个功能性的二分核定位信号（NLS）和染色体区域维护1（CRM 1）依赖的核输出信号（内斯）。输入蛋白α/β和转运蛋白-1被进一步鉴定为JMJD 5相关转运蛋白，并确定了两种核输入受体的不同结合区域。此外，我们还证明了JMJD5的活性NLS和JmjC结构域对于细胞周期蛋白A1的转录都是必需的。染色质免疫沉淀（ChIP）分析证实了组蛋白H3的二甲基化赖氨酸36（H3K36me2）在细胞周期蛋白A1编码区的改变。这些结果表明，N-末端结构域是必不可少的细胞核定位的JMJD 5和其正常的酶功能对底物在核中。(C)2013年Elsevier Masson SAS。All rights reserved.
JMJD5 has recently been reported to participate in circadian rhythm regulation, embryological development, osteoclastogenesis and tumorigenesis. Although JMJD5 has been found mainly localized in the nucleus of cells, how it enters the nucleus remains unclear. Here we report that JMJD5 contains a functional bipartite nuclear localization signal (NLS) and a chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES). Importin alpha/beta and transportin-1 were further identified as JMJD5-associated transport proteins, and different binding regions were determined for the two nuclear import receptors. Additionally, we demonstrate that both the active NLS and the JmjC domain of JMJD5 are necessary for cyclin A1 transcription. Chromatin immunoprecipitation (ChIP) analysis confirmed the alterations of di-methylated lysine 36 of histone H3 (H3K36me2) in the coding region of cyclin A1. These results reveal that the N-terminal domain is essential for the nuclear localization of JMJD5 and its normal enzymatic function towards substrates in the nucleus. (C) 2013 Elsevier Masson SAS. All rights reserved.