Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Biochimie. 2013 Nov;95(11):2114-22. doi: 10.1016/j.biochi.2013.08.002. Epub 2013 Aug 12.
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 α/β 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.
JMJD5 最近被报道参与生物钟节律调节、胚胎发育、破骨细胞生成和肿瘤发生。尽管 JMJD5 主要定位于细胞的核内，但它如何进入核内尚不清楚。在这里，我们报告 JMJD5 含有一个功能性的双组分核定位信号（NLS）和一个依赖于染色体区域维持蛋白 1（CRM1）的核输出信号（NES）。进一步鉴定出 importin α/β 和 transportin-1 是 JMJD5 相关的转运蛋白，并且确定了这两个核输入受体的不同结合区域。此外，我们证明 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 cyclin A1 编码区组蛋白 H3 第 36 位赖氨酸（H3K36me2）的二甲基化变化。这些结果表明，N 端结构域对于 JMJD5 的核定位及其在核内对底物的正常酶功能是必不可少的。
