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ODF2 通过限制 β-连环蛋白的积累来维持中心体的黏合。

ODF2 maintains centrosome cohesion by restricting β-catenin accumulation.

机构信息

Johann-Friedrich-Blumenbach-Institute of Zoology and Anthropology-Developmental Biology, GZMB, Ernst-Caspari-Haus, Justus-von-Liebig-Weg 11, Georg-August-Universität Göttingen, 37077 Göttingen, Germany.

Johann-Friedrich-Blumenbach-Institute of Zoology and Anthropology-Developmental Biology, GZMB, Ernst-Caspari-Haus, Justus-von-Liebig-Weg 11, Georg-August-Universität Göttingen, 37077 Göttingen, Germany

出版信息

J Cell Sci. 2018 Oct 24;131(20):jcs220954. doi: 10.1242/jcs.220954.

Abstract

The centrosome, as the main microtubule-organizing center, safeguards chromosome segregation by supporting the bipolar spindle. Centrosome aberrations are causally related to chromosome segregation disorders, both characterizing cancer cells. Thus, a restriction to only having one centrosome per cell and cell cycle-dependent duplication of the centrosome is mandatory. Duplicated centrosomes remain physically connected, in order to function as a single entity, until onset of mitosis when centrosome disjunction is licensed by disassembly of linker proteins and accumulation of β-catenin. The crucial role β-catenin plays in centrosome disjunction inevitably demands for restricting its premature accumulation. ODF2 (also known as cenexin) is an essential centrosomal component, but its relevance for the interphase centrosome has not been elucidated. We show here that ODF2 plays a central role in centrosome cohesion. Depletion of ODF2 induces premature centrosome splitting and formation of tripolar spindles that are likely caused by the observed accumulation of centrosomal β-catenin. Our data collectively indicate that ODF2 restricts β-catenin accumulation at the centrosome, thus preventing premature centrosome disjunction.

摘要

中心体作为主要的微管组织中心,通过支持双极纺锤体来保障染色体的分离。中心体的异常与染色体分离障碍有关,这两者都是癌细胞的特征。因此,每个细胞和细胞周期中只能有一个中心体,并且中心体的复制是必需的。为了作为一个整体发挥作用,复制的中心体仍然保持物理连接,直到有丝分裂开始,此时通过连接蛋白的解体和β-连环蛋白的积累来许可中心体的分离。β-连环蛋白在中心体分离中起着至关重要的作用,因此必然需要限制其过早积累。ODF2(也称为cenexin)是一个必需的中心体组成部分,但它在有丝分裂间期中心体中的相关性尚未阐明。我们在这里表明,ODF2 在中心体的凝聚中起着核心作用。ODF2 的耗竭会诱导中心体过早分裂,并形成三极纺锤体,这可能是由于观察到的中心体β-连环蛋白的积累所致。我们的数据表明,ODF2 限制了中心体中β-连环蛋白的积累,从而防止了中心体的过早分离。

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