Beclin-1 is required for chromosome congression and proper outer kinetochore assembly
Beclin-1 is required for chromosome congression and proper outer kinetochore assembly
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DOI：
10.1038/embor.2013.23
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发表时间：
2013-04-01
期刊：
影响因子：
7.7
通讯作者：
Berlioz-Torrent, Clarisse
中科院分区：
文献类型：
--
作者：
Fremont, Stephane;Gerard, Annabelle;Berlioz-Torrent, Clarisse
Beclin-1在巨噬细胞自噬、肿瘤发生和胞质分裂中的作用被认为是通过与PI3K-III复合体的结合而实现的。在这里，我们描述了Beclin-1在有丝分裂染色体收缩中的一个新角色，它独立于PI3K-III复合体，以及它在自噬中的作用。HeLa细胞中的Beclin-1缺失导致外动粒蛋白CENP-E、CENP-F和ZW10的显著减少，从而导致细胞出现严重的染色体聚集问题。BEKLIN-1与着丝粒微管结合，在附着的染色体着丝点附近形成离散的焦点。我们发现Beclin-1直接与KMN(Knl-1/Mis12/Ndc80)复合体的一个成分Zwint-1相互作用，这对动粒-微管相互作用是必不可少的。这表明Beclin-1作用于KMN复合体的下游，影响外部动粒蛋白的募集，并在有丝分裂过程中促进动粒准确锚定在纺锤体上。
The functions of Beclin-1 in macroautophagy, tumorigenesis and cytokinesis are thought to be mediated by its association with the PI3K-III complex. Here, we describe a new role for Beclin-1 in mitotic chromosome congression that is independent of the PI3K-III complex and its role in autophagy. Beclin-1 depletion in HeLa cells leads to a significant reduction of the outer kinetochore proteins CENP-E, CENP-F and ZW10, and, consequently, the cells present severe problems in chromosome congression. Beclin-1 associates with kinetochore microtubules and forms discrete foci near the kinetochores of attached chromosomes. We show that Beclin-1 interacts directly with Zwint-1-a component of the KMN (KNL-1/Mis12/Ndc80) complex-which is essential for kinetochore-microtubule interactions. This suggests that Beclin-1 acts downstream of the KMN complex to influence the recruitment of outer kinetochore proteins and promotes accurate kinetochore anchoring to the spindle during mitosis.