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

被引：43

作者：

Fremont, Stephane ^{[1
,2
,3
,4
]}

Gerard, Annabelle ^{[1
,2
,3
]}

Gallouxw, Marie ^{[1
,2
,3
]}

Janvier, Katy ^{[1
,2
,3
]}

Karess, Roger E. ^{[4
,5
]}

Berlioz-Torrent, Clarisse ^{[1
,2
,3
]}

机构：

[1] Inst Cochin, INSERM, U1016, F-75014 Paris, France

[2] CNRS, UMR8104, F-75014 Paris, France

[3] Univ Paris 05, F-75014 Paris, France

[4] Univ Paris Diderot, F-75013 Paris, France

[5] CNRS, UMR 7592, Inst Jacques Monod, F-75013 Paris, France

来源：

EMBO REPORTS | 2013年 / 14卷 / 04期

关键词：

Beclin-1; chromosome congression; kinetochore assembly; mitosis; Zwint-1; COMPLEX; AUTOPHAGY; ZWINT-1; PHOSPHORYLATION; CYTOKINESIS; PROGRESSION; RUBICON; ATG14L; VPS34; ZW10;

D O I：

10.1038/embor.2013.23

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：364 / 372

页数：9

共 24 条

[1] Ubiquitination and phosphorylation of Beclin 1 and its binding partners: Tuning class III phosphatidylinositol 3-kinase activity and tumor suppression [J].

Abrahamsen, Hilde ;

Stenmark, Harald ;

Platta, Harald W. .

FEBS LETTERS, 2012, 586 (11) :1584-1591

[2] Network organization of the human autophagy system [J].

Behrends, Christian ;

Sowa, Mathew E. ;

Gygi, Steven P. ;

Harper, J. Wade .

NATURE, 2010, 466 (7302) :68-U84

[3] Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F [J].

Bomont, P ;

Maddox, P ;

Shah, JV ;

Desai, AB ;

Cleveland, DW .

EMBO JOURNAL, 2005, 24 (22) :3927-3939

[4] Molecular architecture of the kinetochore-microtubule interface [J].

Cheeseman, Iain M. ;

Desai, Arshad .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (01) :33-46

[5] A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension [J].

Cheeseman, IM ;

Niessen, S ;

Anderson, S ;

Hyndman, F ;

Yates, JR ;

Oegema, K ;

Desai, A .

GENES & DEVELOPMENT, 2004, 18 (18) :2255-2268

[6] The Beclin 1-VPS34 complex - at the crossroads of autophagy and beyond [J].

Funderburk, Sarah F. ;

Wang, Qing Jun ;

Yue, Zhenyu .

TRENDS IN CELL BIOLOGY, 2010, 20 (06) :355-362

[7] Negative Regulation of Vps34 by Cdk Mediated Phosphorylation [J].

Furuya, Tsuyoshi ;

Kim, Minsu ;

Lipinski, Marta ;

Li, Juying ;

Kim, Dohoon ;

Lu, Tao ;

Shen, Yong ;

Rameh, Lucia ;

Yankner, Bruce ;

Tsai, Li-Huei ;

Yuan, Junying .

MOLECULAR CELL, 2010, 38 (04) :500-511

[8] The Beclin 1 interactome [J].

He, Congcong ;

Levine, Beth .

CURRENT OPINION IN CELL BIOLOGY, 2010, 22 (02) :140-149

[9] The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo [J].

Joseph, J ;

Liu, ST ;

Jablonski, SA ;

Yen, TJ ;

Dasso, M .

CURRENT BIOLOGY, 2004, 14 (07) :611-617

[10] ZW10 links mitotic checkpoint signaling to the structural kinetochore [J].

Kops, GJPL ;

Kim, Y ;

Weaver, BAA ;

Mao, YH ;

McLeod, I ;

Yates, JR ;

Tagaya, M ;

Cleveland, DW .

JOURNAL OF CELL BIOLOGY, 2005, 169 (01) :49-60

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