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HES1是范可尼贫血核心复合体的一种新型相互作用蛋白。

HES1 is a novel interactor of the Fanconi anemia core complex.

作者信息

Tremblay Cédric S, Huang Feng F, Habi Ouassila, Huard Caroline C, Godin Chantal, Lévesque Georges, Carreau Madeleine

机构信息

Unité de recherche en Pédiatrie, Centre de recherche du Centre Hospitalier de l'Université Laval, Québec, Canada.

出版信息

Blood. 2008 Sep 1;112(5):2062-70. doi: 10.1182/blood-2008-04-152710. Epub 2008 Jun 11.

Abstract

Fanconi anemia (FA) proteins are thought to play a role in chromosome stability and repair of DNA cross-links; however, these functions may not fully explain the developmental abnormalities and bone marrow failure that are characteristic of FA individuals. Here we associate the FA proteins with the Notch1 developmental pathway through a direct protein-protein interaction between the FA core complex and the hairy enhancer of split 1 (HES1). HES1 interaction with FA core complex members is dependent on a functional FA pathway. Cells depleted of HES1 exhibit an FA-like phenotype that includes cellular hypersensitivity to mitomycin C (MMC) and lack of FANCD2 monoubiquitination and foci formation. HES1 is also required for proper nuclear localization or stability of some members of the core complex. Our results suggest that HES1 is a novel interacting protein of the FA core complex.

摘要

范可尼贫血(FA)蛋白被认为在染色体稳定性和DNA交联修复中发挥作用;然而,这些功能可能无法完全解释FA患者所特有的发育异常和骨髓衰竭。在这里,我们通过FA核心复合物与分裂增强子1(HES1)之间的直接蛋白质-蛋白质相互作用,将FA蛋白与Notch1发育途径联系起来。HES1与FA核心复合物成员的相互作用依赖于功能性FA途径。缺乏HES1的细胞表现出类似FA的表型,包括对丝裂霉素C(MMC)的细胞超敏反应以及缺乏FANCD2单泛素化和灶形成。HES1对于核心复合物某些成员的正确核定位或稳定性也是必需的。我们的结果表明,HES1是FA核心复合物的一种新型相互作用蛋白。

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