![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 16, Issue 10, 4609-4622, October 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Section of Molecular and Cellular Biology, University of California–Davis, Davis, CA 95616
Submitted March 28, 2005;
Accepted July 11, 2005
Monitoring Editor: Trisha Davis
Recently, we have shown that a cancer causing truncation in adenomatous polyposis coli (APC) (APC1–1450) dominantly interferes with mitotic spindle function, suggesting APC regulates microtubule dynamics during mitosis. Here, we examine the possibility that APC mutants interfere with the function of EB1, a plus-end microtubule-binding protein that interacts with APC and is required for normal microtubule dynamics. We show that siRNA-mediated inhibition of APC, EB1, or APC and EB1 together give rise to similar defects in mitotic spindles and chromosome alignment without arresting cells in mitosis; in contrast inhibition of CLIP170 or LIS1 cause distinct spindle defects and mitotic arrest. We show that APC1–1450 acts as a dominant negative by forming a hetero-oligomer with the full-length APC and preventing it from interacting with EB1, which is consistent with a functional relationship between APC and EB1. Live-imaging of mitotic cells expressing EB1-GFP demonstrates that APC1–1450 compromises the dynamics of EB1-comets, increasing the frequency of EB1-GFP pausing. Together these data provide novel insight into how APC may regulate mitotic spindle function and how errors in chromosome segregation are tolerated in tumor cells.
Abbreviations used: ACA, anti-centromere antibody; APC, adenomatous polyposis coli; CIN, chromosome instability; CLIP170, cytoplasmic linker protein 170; EB1, end binding 1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IP, immunoprecipitation; KAP3a, kinesin-associated protein 3a; LIS1, lissencephaly 1; siRNA, small interfering RNA; +TIPs, plus-end tracking protein.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Kenneth B. Kaplan (kbkaplan{at}ucdavis.edu).
This article has been cited by other articles:
|
|
 |
|
  Z. Li, K. Kroboth, I. P. Newton, and I. S. Nathke Novel self-association of the APC molecule affects APC clusters and cell migration J. Cell Sci., June 1, 2008; 121(11): 1916 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Rusan and M. Peifer Original CIN: reviewing roles for APC in chromosome instability J. Cell Biol., May 28, 2008; 181(5): 719 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sun, J. Gao, X. Dong, M. Liu, D. Li, X. Shi, J.-T. Dong, X. Lu, C. Liu, and J. Zhou EB1 promotes Aurora-B kinase activity through blocking its inactivation by protein phosphatase 2A PNAS, May 20, 2008; 105(20): 7153 - 7158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q.-X. Yue, Z.-W. Cao, S.-H. Guan, X.-H. Liu, L. Tao, W.-Y. Wu, Y.-X. Li, P.-Y. Yang, X. Liu, and D.-A. Guo Proteomics Characterization of the Cytotoxicity Mechanism of Ganoderic Acid D and Computer-automated Estimation of the Possible Drug Target Network Mol. Cell. Proteomics, May 1, 2008; 7(5): 949 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Buttrick, L. M.A. Beaumont, J. Leitch, C. Yau, J. R. Hughes, and J. G. Wakefield Akt regulates centrosome migration and spindle orientation in the early Drosophila melanogaster embryo J. Cell Biol., February 6, 2008; 180(3): 537 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Bisgrove, Y.-R. J. Lee, B. Liu, N. T. Peters, and D. L. Kropf The Microtubule Plus-End Binding Protein EB1 Functions in Root Responses to Touch and Gravity Signals in Arabidopsis PLANT CELL, February 1, 2008; 20(2): 396 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Fleming, M. Zajac, D. M. Moschenross, D. C. Montrose, D. W. Rosenberg, A. E. Cowan, and J. S. Tirnauer Planar Spindle Orientation and Asymmetric Cytokinesis in the Mouse Small Intestine J. Histochem. Cytochem., November 1, 2007; 55(11): 1173 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Aoki and M. M. Taketo Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene J. Cell Sci., October 1, 2007; 120(19): 3327 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Caldwell, R. A. Green, and K. B. Kaplan APC mutations lead to cytokinetic failures in vitro and tetraploid genotypes in Min mice J. Cell Biol., September 24, 2007; 178(7): 1109 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, S. Ahmad, and Y. Mao BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment J. Cell Biol., August 27, 2007; 178(5): 773 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Arasaki, K. Tani, T. Yoshimori, D. J. Stephens, and M. Tagaya Nordihydroguaiaretic Acid Affects Multiple Dynein-Dynactin Functions in Interphase and Mitotic Cells Mol. Pharmacol., February 1, 2007; 71(2): 454 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dikovskaya, D. Schiffmann, I. P. Newton, A. Oakley, K. Kroboth, O. Sansom, T. J. Jamieson, V. Meniel, A. Clarke, and I. S. Nathke Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis J. Cell Biol., January 16, 2007; 176(2): 183 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cuschieri, R. Miller, and J. Vogel {gamma}-Tubulin Is Required for Proper Recruitment and Assembly of Kar9-Bim1 Complexes in Budding Yeast Mol. Biol. Cell, October 1, 2006; 17(10): 4420 - 4434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Pereira, A. J. Pereira, A. R.R. Maia, K. Drabek, C. L. Sayas, P. J. Hergert, M. Lince-Faria, I. Matos, C. Duque, T. Stepanova, et al. Mammalian CLASP1 and CLASP2 Cooperate to Ensure Mitotic Fidelity by Regulating Spindle and Kinetochore Function Mol. Biol. Cell, October 1, 2006; 17(10): 4526 - 4542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. McCartney, M. H. Price, R. L. Webb, M. A. Hayden, L. M. Holot, M. Zhou, A. Bejsovec, and M. Peifer Testing hypotheses for the functions of APC family proteins using null and truncation alleles in Drosophila Development, June 15, 2006; 133(12): 2407 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Wolyniak, K. Blake-Hodek, K. Kosco, E. Hwang, L. You, and T. C. Huffaker The Regulation of Microtubule Dynamics in Saccharomyces cerevisiae by Three Interacting Plus-End Tracking Proteins Mol. Biol. Cell, June 1, 2006; 17(6): 2789 - 2798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kita, T. Wittmann, I. S. Nathke, and C. M. Waterman-Storer Adenomatous Polyposis Coli on Microtubule Plus Ends in Cell Extensions Can Promote Microtubule Net Growth with or without EB1 Mol. Biol. Cell, May 1, 2006; 17(5): 2331 - 2345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. McGee, R. Rillo, A. S. Anderson, and D. A. Starr UNC-83 Is a KASH Protein Required for Nuclear Migration and Is Recruited to the Outer Nuclear Membrane by a Physical Interaction with the SUN Protein UNC-84 Mol. Biol. Cell, April 1, 2006; 17(4): 1790 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hannak and R. Heald Xorbit/CLASP links dynamic microtubules to chromosomes in the Xenopus meiotic spindle J. Cell Biol., January 3, 2006; 172(1): 19 - 25. [Abstract] [Full Text] [PDF]
|
|
