Inserm, U1016, Institut Cochin, 27, Rue du faubourg Saint Jacques, 75014 Paris, France.
EMBO Rep. 2013 Apr;14(4):364-72. doi: 10.1038/embor.2013.23. Epub 2013 Mar 12.
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.
Beclin-1 在巨自噬、肿瘤发生和细胞分裂中的功能被认为是通过其与 PI3K-III 复合物的关联来介导的。在这里，我们描述了 Beclin-1 在有丝分裂染色体向心性收缩中的一个新作用，该作用独立于 PI3K-III 复合物及其在自噬中的作用。HeLa 细胞中 Beclin-1 的耗竭导致外着丝粒蛋白 CENP-E、CENP-F 和 ZW10 的显著减少，因此，细胞在染色体向心性收缩方面存在严重问题。Beclin-1 与着丝粒微管结合，并在附着染色体的着丝粒附近形成离散焦点。我们表明，Beclin-1 与 Zwint-1 直接相互作用 - KMN（KNL-1/Mis12/Ndc80 复合物）复合物的一个组成部分-对于着丝粒微管相互作用是必不可少的。这表明 Beclin-1 作为 KMN 复合物的下游因子发挥作用，影响外着丝粒蛋白的募集，并在有丝分裂过程中促进着丝粒与纺锤体的准确锚定。
