Regulation of Borealin by Phosphorylation at Serine 219
Regulation of Borealin by Phosphorylation at Serine 219
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DOI：
10.1002/jcb.22853
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Taylor, William R.
中科院分区：
文献类型：
--
作者：
Kaur, Harpreet;Bekier, Mike E.;Taylor, William R.
由Borealin、INCENP、Survivin和Aurora B组成的染色体乘客复合物遵循动态定位模式，以发挥其作为染色体排列、纺锤体组装检查点和胞质分裂的调节剂的作用。染色体乘客蛋白的翻译后修饰在调节复合物的定位和功能中起重要作用。由于磷酸化作用，Borealin在有丝分裂过程中显示出较慢的电泳迁移率。在这里，我们表明，在S219磷酸化是负责这种流动性的转变。不能在该位点磷酸化的Borealin的S219 A突变体显示着丝粒定位缺陷，这在用诺考达唑阻滞有丝分裂的细胞中是明显的。此外，S219 A形式的Borealin不能有效地挽救内源性蛋白质敲低后发生的有丝分裂缺陷。这些缺陷与表达S219 A形式的Borealin的细胞中着丝粒处Mad 2染色强度的降低相关。这些结果突出了S219处Borealin磷酸化在有丝分裂的适当进展中的重要作用。J.细胞。111：1291-1298，2010. (C)2010 Wiley-Liss，Inc.
The chromosomal passenger complex consisting of Borealin, INCENP, Survivin, and Aurora B follows a dynamic pattern of localization to perform its role as a regulator of chromosome alignment, aspects of the spindle assembly checkpoint, and cytokinesis. Post-translational modifications of chromosomal passenger proteins play an important role in regulating the localization and function of the complex. Borealin displays a slower electrophoretic mobility during mitosis as a result of phosphorylation. Here we show that phosphorylation at S219 is responsible for this mobility shift. An S219A mutant of Borealin that cannot be phosphorylated at this site displays a defect in centromere localization that is evident in cells arrested in mitosis with nocodazole. Further, the S219A form of Borealin is unable to efficiently rescue mitotic defects that occur upon knock-down of the endogenous protein. These defects are correlated with a reduction in the intensity of Mad2 staining at kinetochores in cells expressing the S219A form of Borealin. These results highlight an important role for phosphorylation of Borealin at S219 in the proper progression through mitosis. J. Cell. Biochem. 111: 1291-1298, 2010. (C) 2010 Wiley-Liss, Inc.