Published 11 April 2005. doi:10.1083/jcb.200411118
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 1, 49-60
ZW10 links mitotic checkpoint signaling to the structural kinetochore
Geert J.P.L. Kops1,
Yumi Kim1,
Beth A.A. Weaver1,
Yinghui Mao1,
Ian McLeod2,
John R. Yates, III2,
Mitsuo Tagaya3, and
Don W. Cleveland1
1 Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
2 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037
3 School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan
Correspondence to Don W. Cleveland: dcleveland{at}ucsd.edu
The mitotic checkpoint ensures that chromosomes are divided equally between daughter cells and is a primary mechanism preventing the chromosome instability often seen in aneuploid human tumors. ZW10 and Rod play an essential role in this checkpoint. We show that in mitotic human cells ZW10 resides in a complex with Rod and Zwilch, whereas another ZW10 partner, Zwint-1, is part of a separate complex of structural kinetochore components including Mis12 and Ndc80Hec1. Zwint-1 is critical for recruiting ZW10 to unattached kinetochores. Depletion from human cells or Xenopus egg extracts is used to demonstrate that the ZW10 complex is essential for stable binding of a Mad1Mad2 complex to unattached kinetochores. Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor.
G.J.P.L. Kops's present address is Dept. of Experimental Oncology, UMC Utrecht, 3584 CG Utrecht, Netherlands.
Abbreviations used in this paper: ACA, anti-centromere antiserum; CENP, centromere-associated protein; CSF, cytostatic factor; EYFP, enhanced YFP; KCR, kinetochore-containing region; LAP, localization and affinity purification; siRNA, small interfering RNA; Zwint-1, ZW10-interacting protein 1.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
Related Article
-
Mapping the checkpoint
- Rabiya S. Tuma
J. Cell Biol. 2005 169: 14.
[Full Text]
[PDF]
This article has been cited by other articles:
-
Famulski, J. K., Vos, L., Sun, X., Chan, G.
(2008). Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint. J. Cell Biol.
180: 507-520
[Abstract]
[Full Text]
-
Cheeseman, I. M., Hori, T., Fukagawa, T., Desai, A.
(2008). KNL1 and the CENP-H/I/K Complex Coordinately Direct Kinetochore Assembly in Vertebrates. Mol. Biol. Cell
19: 587-594
[Abstract]
[Full Text]
-
Sun, Y., Shestakova, A., Hunt, L., Sehgal, S., Lupashin, V., Storrie, B.
(2007). Rab6 Regulates Both ZW10/RINT-1 and Conserved Oligomeric Golgi Complex-dependent Golgi Trafficking and Homeostasis. Mol. Biol. Cell
18: 4129-4142
[Abstract]
[Full Text]
-
Stehman, S. A., Chen, Y., McKenney, R. J., Vallee, R. B.
(2007). NudE and NudEL are required for mitotic progression and are involved in dynein recruitment to kinetochores. J. Cell Biol.
178: 583-594
[Abstract]
[Full Text]
-
Griffis, E. R., Stuurman, N., Vale, R. D.
(2007). Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J. Cell Biol.
177: 1005-1015
[Abstract]
[Full Text]
-
Liang, Y., Yu, W., Li, Y., Yu, L., Zhang, Q., Wang, F., Yang, Z., Du, J., Huang, Q., Yao, X., Zhu, X.
(2007). Nudel Modulates Kinetochore Association and Function of Cytoplasmic Dynein in M Phase. Mol. Biol. Cell
18: 2656-2666
[Abstract]
[Full Text]
-
Perez de Castro, I., de Carcer, G., Malumbres, M.
(2007). A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy. Carcinogenesis
28: 899-912
[Abstract]
[Full Text]
-
Orr, B., Bousbaa, H., Sunkel, C. E.
(2007). Mad2-independent Spindle Assembly Checkpoint Activation and Controlled Metaphase-Anaphase Transition in Drosophila S2 Cells. Mol. Biol. Cell
18: 850-863
[Abstract]
[Full Text]
-
Liu, S.-T., Rattner, J. B., Jablonski, S. A., Yen, T. J.
(2006). Mapping the assembly pathways that specify formation of the trilaminar kinetochore plates in human cells. J. Cell Biol.
175: 41-53
[Abstract]
[Full Text]
-
Varma, D., Dujardin, D. L., Stehman, S. A., Vallee, R. B.
(2006). Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function. J. Cell Biol.
172: 655-662
[Abstract]
[Full Text]
-
Cristea, I. M., Williams, R., Chait, B. T., Rout, M. P.
(2005). Fluorescent Proteins as Proteomic Probes. Mol. Cell. Proteomics
4: 1933-1941
[Abstract]
[Full Text]
-
Siller, K. H., Serr, M., Steward, R., Hays, T. S., Doe, C. Q.
(2005). Live Imaging of Drosophila Brain Neuroblasts Reveals a Role for Lis1/Dynactin in Spindle Assembly and Mitotic Checkpoint Control. Mol. Biol. Cell
16: 5127-5140
[Abstract]
[Full Text]
-
Emanuele, M. J., McCleland, M. L., Satinover, D. L., Stukenberg, P. T.
(2005). Measuring the Stoichiometry and Physical Interactions between Components Elucidates the Architecture of the Vertebrate Kinetochore. Mol. Biol. Cell
16: 4882-4892
[Abstract]
[Full Text]
-
Mao, Y., Desai, A., Cleveland, D. W.
(2005). Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling. J. Cell Biol.
170: 873-880
[Abstract]
[Full Text]