spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 26 Jul 2005
doi: 10.1242/jcs.02487

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.02487v1
118/16/3639    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morrow, C. J.
Right arrow Articles by Taylor, S. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morrow, C. J.
Right arrow Articles by Taylor, S. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

Bub1 and aurora B cooperate to maintain BubR1- mediated inhibition of APC/CCdc20


Christopher J. Morrow, Anthony Tighe, Victoria L. Johnson, Maria I.F. Scott, Claire Ditchfield, and Stephen S. Taylor*
* Author for correspondence (e-mail: stephen.taylor{at}manchester.ac.uk)

The spindle checkpoint maintains genome stability by inhibiting Cdc20-mediated activation of the anaphase promoting complex/cyclosome (APC/C) until all the chromosomes correctly align on the microtubule spindle apparatus via their kinetochores. BubR1, an essential component of this checkpoint, localises to kinetochores and its kinase activity is regulated by the kinesin-related motor protein Cenp-E. BubR1 also inhibits APC/CCdc20 in vitro, thus providing a molecular link between kinetochore-microtubule interactions and the proteolytic machinery that regulates mitotic progression. Several other protein kinases, including Bub1 and members of the Ipl1/aurora family, also regulate anaphase onset. However, in human somatic cells Bub1 and aurora B kinase activity do not appear to be essential for spindle checkpoint function. Specifically, when Bub1 is inhibited by RNA interference, or aurora kinase activity is inhibited with the small molecule ZM447439, cells arrest transiently in mitosis following exposure to spindle toxins that prevent microtubule polymerisation. Here, we show that mitotic arrest of Bub1-deficient cells is dependent on aurora kinase activity, and vice versa. We suggest therefore that the checkpoint is composed of two arms, one dependent on Bub1, the other on aurora B. Analysis of BubR1 complexes suggests that both of these arms converge on the mitotic checkpoint complex (MCC), which includes BubR1, Bub3, Mad2 and Cdc20. Although it is known that MCC components can bind and inhibit the APC/C, we show here for the first time that the binding of the MCC to the APC/C is dependent on an active checkpoint signal. Furthermore, we show that both Bub1 and aurora kinase activity are required to promote binding of the MCC to the APC/C. These observations provide a simple explanation of why BubR1 and Mad2 are essential for checkpoint function following spindle destruction, yet Bub1 and aurora B kinase activity are not. Taken together with other observations, we suggest that these two arms respond to different spindle cues: whereas the Bub1 arm monitors kinetochore-microtubule attachment, the aurora B arm monitors biorientation. This bifurcation in the signalling mechanism may help explain why many tumour cells mount a robust checkpoint response following spindle damage, despite exhibiting chromosome instability.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
R. Heit, J. B. Rattner, G. K. T. Chan, and M. J. Hendzel
G2 histone methylation is required for the proper segregation of chromosomes
J. Cell Sci., August 15, 2009; 122(16): 2957 - 2968.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. E. Bekier, R. Fischbach, J. Lee, and W. R. Taylor
Length of mitotic arrest induced by microtubule-stabilizing drugs determines cell death after mitotic exit
Mol. Cancer Ther., June 1, 2009; 8(6): 1646 - 1654.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
F. Herzog, I. Primorac, P. Dube, P. Lenart, B. Sander, K. Mechtler, H. Stark, and J.-M. Peters
Structure of the Anaphase-Promoting Complex/Cyclosome Interacting with a Mitotic Checkpoint Complex
Science, March 13, 2009; 323(5920): 1477 - 1481.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. W. Wood, P. Chua, D. Sutton, and J. R. Jackson
Centromere-Associated Protein E: A Motor That Puts the Brakes on the Mitotic Checkpoint
Clin. Cancer Res., December 1, 2008; 14(23): 7588 - 7592.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. Tighe, O. Staples, and S. Taylor
Mps1 kinase activity restrains anaphase during an unperturbed mitosis and targets Mad2 to kinetochores
J. Cell Biol., October 21, 2008; 181(6): 893 - 901.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Sczaniecka, A. Feoktistova, K. M. May, J.-S. Chen, J. Blyth, K. L. Gould, and K. G. Hardwick
The Spindle Checkpoint Functions of Mad3 and Mad2 Depend on a Mad3 KEN Box-mediated Interaction with Cdc20-Anaphase-promoting Complex (APC/C)
J. Biol. Chem., August 22, 2008; 283(34): 23039 - 23047.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D.-H. Fu, W. Jiang, J.-T. Zheng, G.-Y. Zhao, Y. Li, H. Yi, Z.-R. Li, J.-D. Jiang, K.-Q. Yang, Y. Wang, et al.
Jadomycin B, an Aurora-B kinase inhibitor discovered through virtual screening
Mol. Cancer Ther., August 1, 2008; 7(8): 2386 - 2393.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Kim, J. Liao, M. L. Dowling, K. R. Voong, S. E. Parker, S. Wang, W. S. El-Deiry, and G. D. Kao
TRAIL Inactivates the Mitotic Checkpoint and Potentiates Death Induced by Microtubule-Targeting Agents in Human Cancer Cells
Cancer Res., May 1, 2008; 68(9): 3440 - 3449.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
E. Logarinho, T. Resende, C. Torres, and H. Bousbaa
The Human Spindle Assembly Checkpoint Protein Bub3 Is Required for the Establishment of Efficient Kinetochore-Microtubule Attachments
Mol. Biol. Cell, April 1, 2008; 19(4): 1798 - 1813.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
O. K. Wong and G. Fang
Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope
J. Cell Biol., November 19, 2007; 179(4): 611 - 617.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
F. Yang, D. G. Camp II, M. A. Gritsenko, Q. Luo, R. T. Kelly, T. R. W. Clauss, W. R. Brinkley, R. D. Smith, and D. L. Stenoien
Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus
J. Cell Sci., November 15, 2007; 120(22): 4060 - 4070.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
B. Williams, G. Leung, H. Maiato, A. Wong, Z. Li, E. V. Williams, C. Kirkpatrick, C. F. Aquadro, C. L. Rieder, and M. L. Goldberg
Mitch a rapidly evolving component of the Ndc80 kinetochore complex required for correct chromosome segregation in Drosophila
J. Cell Sci., October 15, 2007; 120(20): 3522 - 3533.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Matsumura, F. Toyoshima, and E. Nishida
Polo-like Kinase 1 Facilitates Chromosome Alignment during Prometaphase through BubR1
J. Biol. Chem., May 18, 2007; 282(20): 15217 - 15227.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
E. M.J. King, N. Rachidi, N. Morrice, K. G. Hardwick, and M. J.R. Stark
Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint response to lack of tension at kinetochores
Genes & Dev., May 15, 2007; 21(10): 1163 - 1168.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. Braunstein, S. Miniowitz, Y. Moshe, and A. Hershko
Inhibitory factors associated with anaphase-promoting complex/cylosome in mitotic checkpoint
PNAS, March 20, 2007; 104(12): 4870 - 4875.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Bhati, Y. Gokmen-Polar, G. W. Sledge Jr., C. Fan, H. Nakshatri, D. Ketelsen, C. H. Borchers, M. J. Dial, C. Patterson, and N. Klauber-DeMore
2-Methoxyestradiol Inhibits the Anaphase-Promoting Complex and Protein Translation in Human Breast Cancer Cells
Cancer Res., January 15, 2007; 67(2): 702 - 708.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
J. Fu, M. Bian, Q. Jiang, and C. Zhang
Roles of Aurora Kinases in Mitosis and Tumorigenesis
Mol. Cancer Res., January 1, 2007; 5(1): 1 - 10.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
F. Girdler, K. E. Gascoigne, P. A. Eyers, S. Hartmuth, C. Crafter, K. M. Foote, N. J. Keen, and S. S. Taylor
Validating Aurora B as an anti-cancer drug target
J. Cell Sci., September 1, 2006; 119(17): 3664 - 3675.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. J. Holland and S. S. Taylor
Cyclin-B1-mediated inhibition of excess separase is required for timely chromosome disjunction
J. Cell Sci., August 15, 2006; 119(16): 3325 - 3336.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
K. Wolanin, A. Magalska, G. Mosieniak, R. Klinger, S. McKenna, S. Vejda, E. Sikora, and K. Piwocka
Curcumin Affects Components of the Chromosomal Passenger Complex and Induces Mitotic Catastrophe in Apoptosis-Resistant Bcr-Abl-Expressing Cells
Mol. Cancer Res., July 1, 2006; 4(7): 457 - 469.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
H. A Homer, A. McDougall, M. Levasseur, A. P Murdoch, and M. Herbert
Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes
Reproduction, December 1, 2005; 130(6): 829 - 843.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. V. Holt, M. A. S. Vergnolle, D. Hussein, M. J. Wozniak, V. J. Allan, and S. S. Taylor
Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint
J. Cell Sci., October 15, 2005; 118(20): 4889 - 4900.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005