Beclin-1 is required for chromosome congression and proper outer kinetochore assembly

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. Becli...

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Veröffentlicht in:EMBO reports 2013-04, Vol.14 (4), p.364-372
Hauptverfasser: Frémont, Stéphane, Gérard, Annabelle, Galloux, Marie, Janvier, Katy, Karess, Roger E, Berlioz-Torrent, Clarisse
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Sprache:eng
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Zusammenfassung: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 has a new role independent of the PI3K‐III complex and autophagy. Loss of Beclin‐1 reduces outer kinetochore proteins and causes severe problems in chromosome congression, and its interaction with Zwint‐1 promotes kinetochore–microtubule interactions.
ISSN:1469-221X
1469-3178
DOI:10.1038/embor.2013.23