Grb10 interacts with Bim L and inhibits apoptosis
Grb10 interacts with Bim L and inhibits apoptosis
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DOI：
10.1007/s11033-010-0002-9
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发表时间：
2010-10-01
影响因子：
2.8
通讯作者：
Mao, Yu-min
中科院分区：
文献类型：
--
作者：
Hu, Zhi-qian;Zhang, Jia-yi;Mao, Yu-min
Bim是Bcl-2家族的促凋亡成员，主要参与内在凋亡途径的调节。然而，Bim的促凋亡活性的调节的细节尚未澄清。以Bim L为诱饵，从人胎儿cDNA文库中筛选相互作用蛋白，并鉴定Grb 10为相互作用蛋白。通过共免疫沉淀和细胞内共定位研究验证了这种相互作用。通过酵母交配试验鉴定了Bim L结合Grb 10的潜在片段。Grb 10与Bim的动力蛋白结合域（dynein binding domain，DBD）相互作用，抑制过表达含有Bim异构体的DBD所引发的细胞凋亡。Bim的DBD上的推定磷酸化位点对Grb 10的抗促凋亡活性起作用。我们的研究结果表明，Grb 10与Bim L相互作用，抑制其促凋亡活性的磷酸化依赖的方式。
Bim is a proapoptotic member of the Bcl-2 family and is primarily involved in the regulation of the intrinsic apoptotic pathway. However, the detail of regulation of Bim's proapoptotic activity has not been clarified yet. Using Bim L as bait, we screened a human fetal cDNA library for interacting proteins and identified Grb10 as an interactor. This interaction was verified by co-immuno-precipitation and intracellular co-localization studies. The potential segment of Bim L that binds Grb10 was identified via a yeast mating test. Grb10 interacted with the DBD (dynein binding domain) of Bim and inhibited apoptosis triggered by overexpression of DBD containing Bim isoforms. The putative phosphorylation sites on DBD of Bim play a role for the anti-proapoptotic activity of Grb10. Our results suggest that Grb10 interacts with Bim L and inhibits its proapoptotic activity in a phosphorylation-dependant manner.