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Grb10 interacts with Bim L and inhibits apoptosis
Authors:Zhi-qian Hu  Jia-yi Zhang  Chao-neng Ji  Yi Xie  Jin-zhong Chen  Yu-min Mao
Affiliation:(1) State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, 200433, People’s Republic of China;(2) Department of Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China;
Abstract: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-immunoprecipitation 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.
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