Arsenate-mediated G2 cell cycle arrest in U-2OS cells involves phosphorylation of human polycomb protein 2 by p38 MAPK
Arsenate-mediated G2 cell cycle arrest in U-2OS cells involves phosphorylation of human polycomb protein 2 by p38 MAPK
复制标题
U-2OS 细胞中砷酸盐介导的 G2 细胞周期停滞涉及 p38 MAPK 对人多梳蛋白 2 的磷酸化
DOI：
10.1002/1873-3468.13272
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发表时间：
2018-12-01
期刊：
影响因子：
3.5
通讯作者：
Zhao，Ming
中科院分区：
文献类型：
--
作者：
Wu，Wei;Zhou，Hui;Zhao，Ming
G2/M 检查点确保细胞有丝分裂的正确时机。我们之前报道过，p38 丝裂原激活蛋白激酶 (MAPK) 激活对于 U-2OS 骨肉瘤细胞系中应激诱导的 G2 期停滞至关重要，但其分子机制尚不清楚。在这里，使用 T7 噬菌体展示系统，我们发现 p38 直接与人多梳蛋白 2 (HPC2) 结合，并且砷酸盐诱导 U-2OS 细胞中的 G2 停滞是 p38 和 HPC2 磷酸化依赖性的。 HPC2 在苏氨酸 495 处的磷酸化是招募 Ring1 和 Rb 家族蛋白形成多梳抑制复合物 (PRC) 所必需的，而 PRC 是砷酸盐诱导的 CDC2 表达下调所必需的。因此，p38 MAPK 通过 HPC2 磷酸化介导转录抑制来调节细胞周期进程，为砷酸盐诱导的转录沉默提供机制联系。
G2/M checkpoints ensure the proper timing of cell mitosis. We previously reported that p38 mitogen‐activated protein kinase (MAPK) activation is essential for stress‐induced G2 arrest in the U‐2OS osteosarcoma cell line, but the molecular mechanism was obscure. Here, using the T7 phage display system, we find p38 directly binds to human polycomb protein 2 (HPC2), and arsenate‐induced G2 arrest in U‐2OS cell is p38‐ and phosphorylation of HPC2‐dependent. Phosphorylation of HPC2 at threonine 495 is required for recruiting Ring1 and Rb family proteins to form the polycomb repressive complex (PRC), and PRC is required for arsenate‐induced downregulation of CDC2 expression. Thus, p38 MAPK regulates cell cycle progression through phosphorylation of HPC2 to mediate transcriptional repression, providing a mechanistic link for arsenate‐induced transcriptional silencing.