Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 313 (5787): 680-684

Copyright © 2006 by the American Association for the Advancement of Science

Anaphase Inactivation of the Spindle Checkpoint

William J. Palframan,1 Janet B. Meehl,2 Sue L. Jaspersen,3 Mark Winey,2 Andrew W. Murray1*

Abstract: The spindle checkpoint delays cell cycle progression until microtubules attach each pair of sister chromosomes to opposite poles of the mitotic spindle. Following sister chromatid separation, however, the checkpoint ignores chromosomes whose kinetochores are attached to only one spindle pole, a state that activates the checkpoint prior to metaphase. We demonstrate that, in budding yeast, mutual inhibition between the anaphase-promoting complex (APC) and Mps1, an essential component of the checkpoint, leads to sustained inactivation of the spindle checkpoint. Mps1 protein abundance decreases in anaphase, and Mps1 is a target of the APC. Furthermore, expression of Mps1 in anaphase, or repression of the APC in anaphase, reactivates the spindle checkpoint. This APC-Mps1 feedback circuit allows cells to irreversibly inactivate the checkpoint during anaphase.

1 Department of Molecular and Cellular Biology, Biological Laboratories, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
2 MCD Biology, UCB 347, University of Colorado, Boulder, CO 80309, USA.
3 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.

* To whom correspondence should be addressed. E-mail: amurray{at}mcb.harvard.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1.
F. Althoff, R. E. Karess, and C. F. Lehner (2012)
Mol. Biol. Cell 23, 2275-2291
   Abstract »    Full Text »    PDF »
Emerging regulatory mechanisms in ubiquitin-dependent cell cycle control.
A. Mocciaro and M. Rape (2012)
J. Cell Sci. 125, 255-263
   Abstract »    Full Text »    PDF »
A quantitative model for cyclin-dependent kinase control of the cell cycle: revisited.
F. Uhlmann, C. Bouchoux, and S. Lopez-Aviles (2011)
Phil Trans R Soc B 366, 3572-3583
   Abstract »    Full Text »    PDF »
Ubiquitin Ligase Ufd2 Is Required for Efficient Degradation of Mps1 Kinase.
C. Liu, D. van Dyk, V. Choe, J. Yan, S. Majumder, M. Costanzo, X. Bao, C. Boone, K. Huo, M. Winey, et al. (2011)
J. Biol. Chem. 286, 43660-43667
   Abstract »    Full Text »    PDF »
System-level feedbacks make the anaphase switch irreversible.
E. He, O. Kapuy, R. A. Oliveira, F. Uhlmann, J. J. Tyson, and B. Novak (2011)
PNAS 108, 10016-10021
   Abstract »    Full Text »    PDF »
Phosphorylation of the Anaphase-promoting Complex/Cdc27 Is Involved in TGF-{beta} Signaling.
L. Zhang, T. Fujita, G. Wu, X. Xiao, and Y. Wan (2011)
J. Biol. Chem. 286, 10041-10050
   Abstract »    Full Text »    PDF »
Splitting the Nucleus: What's Wrong with the Tripartite Ring Model?.
K. Nasmyth and R. A. Oliveira (2011)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Cellular Abundance of Mps1 and the Role of Its Carboxyl Terminal Tail in Substrate Recruitment.
T. Sun, X. Yang, W. Wang, X. Zhang, Q. Xu, S. Zhu, R. Kuchta, G. Chen, and X. Liu (2010)
J. Biol. Chem. 285, 38730-38739
   Abstract »    Full Text »    PDF »
Antizyme Restrains Centrosome Amplification by Regulating the Accumulation of Mps1 at Centrosomes.
C. Kasbek, C.-H. Yang, and H. A. Fisk (2010)
Mol. Biol. Cell 21, 3878-3889
   Abstract »    Full Text »    PDF »
Degradation of the Human Mitotic Checkpoint Kinase Mps1 Is Cell Cycle-regulated by APC-cCdc20 and APC-cCdh1 Ubiquitin Ligases.
Y. Cui, X. Cheng, C. Zhang, Y. Zhang, S. Li, C. Wang, and T. M. Guadagno (2010)
J. Biol. Chem. 285, 32988-32998
   Abstract »    Full Text »    PDF »
APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome.
G. J. P. L. Kops, M. van der Voet, M. S. Manak, M. H. J. van Osch, S. M. Naini, A. Brear, I. X. McLeod, D. M. Hentschel, J. R. Yates III, S. van den Heuvel, et al. (2010)
J. Cell Sci. 123, 1623-1633
   Abstract »    Full Text »    PDF »
Protein phosphatase 2A contributes to separase regulation and the co-ordination of anaphase.
C. P. Wardlaw (2010)
Bioscience Horizons 3, 66-76
   Abstract »    Full Text »    PDF »
Overcoming inhibition in the spindle checkpoint.
V. Vanoosthuyse and K. G. Hardwick (2009)
Genes & Dev. 23, 2799-2805
   Abstract »    Full Text »    PDF »
Mlp1 Acts as a Mitotic Scaffold to Spatially Regulate Spindle Assembly Checkpoint Proteins in Aspergillus nidulans.
C. P. De Souza, S. B. Hashmi, T. Nayak, B. Oakley, and S. A. Osmani (2009)
Mol. Biol. Cell 20, 2146-2159
   Abstract »    Full Text »    PDF »
Requirements for Protein Phosphorylation and the Kinase Activity of Polo-like Kinase 1 (Plk1) for the Kinetochore Function of Mitotic Arrest Deficiency Protein 1 (Mad1).
Y.-H. Chi, K. Haller, M. D. Ward, O. J. Semmes, Y. Li, and K.-T. Jeang (2008)
J. Biol. Chem. 283, 35834-35844
   Abstract »    Full Text »    PDF »
Regulation of the Anaphase-promoting Complex-Separase Cascade by Transforming Growth Factor-{beta} Modulates Mitotic Progression in Bone Marrow Stromal Cells.
T. Fujita, M. W. Epperly, H. Zou, J. S. Greenberger, and Y. Wan (2008)
Mol. Biol. Cell 19, 5446-5455
   Abstract »    Full Text »    PDF »
Pseudosubstrate Inhibition of the Anaphase-Promoting Complex by Acm1: Regulation by Proteolysis and Cdc28 Phosphorylation.
D. Ostapenko, J. L. Burton, R. Wang, and M. J. Solomon (2008)
Mol. Cell. Biol. 28, 4653-4664
   Abstract »    Full Text »    PDF »
Spindle checkpoint activation at meiosis I advances anaphase II onset via meiosis-specific APC/C regulation.
A. Yamamoto, K. Kitamura, D. Hihara, Y. Hirose, S. Katsuyama, and Y. Hiraoka (2008)
J. Cell Biol. 182, 277-288
   Abstract »    Full Text »    PDF »
Preventing the Degradation of Mps1 at Centrosomes Is Sufficient to Cause Centrosome Reduplication in Human Cells.
C. Kasbek, C.-H. Yang, A. M. Yusof, H. M. Chapman, M. Winey, and H. A. Fisk (2007)
Mol. Biol. Cell 18, 4457-4469
   Abstract »    Full Text »    PDF »
Mps1 Activation Loop Autophosphorylation Enhances Kinase Activity.
C. P. Mattison, W. M. Old, E. Steiner, B. J. Huneycutt, K. A. Resing, N. G. Ahn, and M. Winey (2007)
J. Biol. Chem. 282, 30553-30561
   Abstract »    Full Text »    PDF »
KEN-Box-dependent Degradation of the Bub1 Spindle Checkpoint Kinase by the Anaphase-promoting Complex/Cyclosome.
W. Qi and H. Yu (2007)
J. Biol. Chem. 282, 3672-3679
   Abstract »    Full Text »    PDF »
The spindle checkpoint.
K. M. May and K. G. Hardwick (2006)
J. Cell Sci. 119, 4139-4142
   Full Text »    PDF »
Cell biology. Extinguishing a cell cycle checkpoint..
M. A. Hoyt (2006)
Science 313, 624-625
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882