Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

被引:166
作者
Saurin, Adrian T. [1 ]
van der Waal, Maike S. [2 ]
Medema, Rene H. [2 ]
Lens, Susanne M. A. [2 ]
Kops, Geert J. P. L. [1 ]
机构
[1] Univ Med Ctr Utrecht, Mol Canc Res & Canc Genom Ctr, NL-3584 CG Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Dept Med Oncol, NL-3584 CG Utrecht, Netherlands
来源
NATURE COMMUNICATIONS | 2011年 / 2卷
基金
欧洲研究理事会;
关键词
ANAPHASE-PROMOTING COMPLEX/CYCLOSOME; KINETOCHORE-MICROTUBULE ATTACHMENT; CHROMOSOMAL PASSENGER COMPLEX; SPINDLE-ASSEMBLY CHECKPOINT; MITOTIC CHECKPOINT; CENP-E; KINASE; MAD2; DYNAMICS; BUBR1;
D O I
10.1038/ncomms1319
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis.
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页数:9
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共 42 条
  • [1] Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint
    Brito, Daniela A.
    Rieder, Conly L.
    [J]. CURRENT BIOLOGY, 2006, 16 (12) : 1194 - 1200
  • [2] The conserved KMN network constitutes the core microtubule-binding site of the kinetochore
    Cheeseman, Iain M.
    Chappie, Joshua S.
    Wilson-Kubalek, Elizabeth M.
    Desai, Arshad
    [J]. CELL, 2006, 127 (05) : 983 - 997
  • [3] Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex
    Ciferri, Claudio
    Pasqualato, Sebastiano
    Screpanti, Emanuela
    Varetti, Gianluca
    Santaguida, Stefano
    Dos Reis, Gabriel
    Maiolica, Alessio
    Polka, Jessica
    De Luca, Jennifer G.
    De Wulf, Peter
    Salek, Mogjiborahman
    Rappsilber, Juri
    Moores, Carolyn A.
    Salmon, Edward D.
    Musacchio, Andrea
    [J]. CELL, 2008, 133 (03) : 427 - 439
  • [4] Temporal and spatial control of cyclin B1 destruction in metaphase
    Clute, P
    Pines, J
    [J]. NATURE CELL BIOLOGY, 1999, 1 (02) : 82 - 87
  • [5] Kinetochore microtubule dynamics and attachment stability are regulated by Hec1
    DeLuca, Jennifer G.
    Gall, Walter E.
    Ciferri, Claudio
    Cimini, Daniela
    Musacchio, Andrea
    Salmon, E. D.
    [J]. CELL, 2006, 127 (05) : 969 - 982
  • [6] Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores
    DeLuca, JG
    Howell, BJ
    Canman, JC
    Hickey, JM
    Fang, GW
    Salmon, ED
    [J]. CURRENT BIOLOGY, 2003, 13 (23) : 2103 - 2109
  • [7] Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores
    Ditchfield, C
    Johnson, VL
    Tighe, A
    Ellston, R
    Haworth, C
    Johnson, T
    Mortlock, A
    Keen, N
    Taylor, SS
    [J]. JOURNAL OF CELL BIOLOGY, 2003, 161 (02) : 267 - 280
  • [8] MAD3 encodes a novel component of the spindle checkpoint which interacts with Bub3p, Cdc20p, and Mad2p
    Hardwick, KC
    Johnston, RC
    Smith, DL
    Murray, AW
    [J]. JOURNAL OF CELL BIOLOGY, 2000, 148 (05) : 871 - 882
  • [9] The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint
    Hauf, S
    Cole, RW
    LaTerra, S
    Zimmer, C
    Schnapp, G
    Walter, R
    Heckel, A
    van Meel, J
    Rieder, CL
    Peters, JM
    [J]. JOURNAL OF CELL BIOLOGY, 2003, 161 (02) : 281 - 294
  • [10] Structure of the Anaphase-Promoting Complex/Cyclosome Interacting with a Mitotic Checkpoint Complex
    Herzog, Franz
    Primorac, Ivana
    Dube, Prakash
    Lenart, Peter
    Sander, Bjoern
    Mechtler, Karl
    Stark, Holger
    Peters, Jan-Michael
    [J]. SCIENCE, 2009, 323 (5920) : 1477 - 1481