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Nuclear membrane protein emerin: roles in gene regulation, actin dynamics and human disease

机译:核膜蛋白emerin:基因调控中的作用,肌动蛋白动态和人类疾病

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Loss of emerin, a nuclear membrane protein, causes Emery-Dreifuss muscular dystrophy (EDMD), characterized by muscle weakening, contractures of major tendons and potentially lethal cardiac conduction system defects. Emerin has a LEM-domain and therefore binds barrier-to-autointegration factor (BAF), a conserved chromatin protein essential for cell division. BAF recruits emerin to chromatin and regulates higher-order chromatin structure during nuclear assembly. Emerin also binds filaments formed by A-type lamins, mutations in which also cause EDMD. Other partners for emerin include nesprin-la and transcriptional regulators such as germ cell-less (GCL). The binding affinities of these partners range from 4nM (nesprin-la) to 200 nM (BAF), and are physiologically significant. Biochemical studies therefore provide a valid means to predict the properties of emerin-lamin complexes in vivo. Emerin and lamin A together form stable complexes with either BAF or GCL in vitro. BAF, however, competes with GCL for binding to emerin in vitro. These and additional partners, notably actin and nuclear myosin I, suggest disease-relevant roles for emerin in gene regulation and the mechanical integrity of the nucleus.
机译:核膜蛋白失去核膜蛋白,导致肌射肌营养不良(EDMD),其特征在于肌肉削弱,主要肌腱挛缩和潜在的致命心脏传导系统缺陷。 Emerin具有LEM结构域,因此结合障碍对自身抗组成因子(BAF),是细胞分裂必需的保守染色质蛋白。 BAF为染色质募集染色体,并在核组件期间调节高阶染色质结构。 Emerin还结合由型层状形成的长丝,其突变也引起EDMD。 Emerin的其他合作伙伴包括Nesprin-La和转录调节剂,如胚芽细胞(GCL)。这些合作伙伴的结合亲和力范围为4nm(nesprin-la)至200nm(baf),并且在生理上显着。因此,生物化学研究提供了预测体内Emerin-Lamin络合物的性质的有效手段。 Emerin和Lamin A一起形成稳定的复合物,其中包含BAF或GCl体外。然而,BAF与GCL竞争,用于在体外与Emerin结合。这些和额外的合作伙伴,特别是肌动蛋白和核肌球蛋白I,表明了在基因调节中具有疾病相关的作用以及细胞核的机械完整性。

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