title: Beclin-1 is required for chromosome congression and proper outer kinetochore assembly.
abstract: 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.
authors.affiliation: Inserm, U1016, Institut Cochin, 27, Rue du faubourg Saint Jacques, 75014 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Frémont
authors.forename: Annabelle
authors.initials: A
authors.lastname: Gérard
authors.forename: Marie
authors.initials: M
authors.lastname: Galloux
authors.forename: Katy
authors.initials: K
authors.lastname: Janvier
authors.forename: Roger E
authors.initials: RE
authors.lastname: Karess
authors.forename: Clarisse
authors.initials: C
authors.lastname: Berlioz-Torrent
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D000071186:Beclin-1; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D059008:Time-Lapse Imaging
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C413695:ZWINT protein, human