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A role for the Adenomatous Polyposis Coli protein in chromosome segregation

Nature Cell Biology volume 3, pages 429–432 (2001)Cite this article

Abstract

Mutations in the Adenomatous Polyposis Coli (APC) gene are responsible for familial colon cancer and also occur in the early stages of sporadic colon cancer1. APC functions in the Wnt signalling pathway to regulate the degradation of β-catenin (reviewed in refs 1–3). APC also binds to and stabilizes microtubules in vivo and in vitro4, localizes to clusters at the ends of microtubules near the plasma membrane of interphase cells5,6, and is an important regulator of cytoskeletal function7,8. Here we show that cells carrying a truncated APC gene (Min)9 are defective in chromosome segregation. Moreover, during mitosis, APC localizes to the ends of microtubules embedded in kinetochores and forms a complex with the checkpoint proteins Bub1 and Bub3. In vitro, APC is a high-affinity substrate for Bub kinases. Our data are consistent with a role for APC in kinetochore–microtubule attachment and suggest that truncations in APC that eliminate microtubule binding may contribute to chromosomal instability in cancer cells10.

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Figure 1: Cells lacking functional APC protein undergo aberrant mitosis.
Figure 2: APC is localized to kinetochores in mitotic cells.
Figure 3: Bub kinases specifically phosphorylate and bind to APC.
Figure 4: Analysing the role of APC in the mitotic checkpoint.

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Acknowledgements

We thank the Marine Biological Laboratory, R. Weinberg, J. Copeland, the T. J. Mitchison laboratory and the Human Cytogenetics Group at Ninewells Hospital for help, and members of the I.S.N. laboratory and K. Storey for critical reading of the manuscript. A substantial portion of this work was carried out at UC Davis with the support of the American Cancer Society. This work was also supported by grants from the NIH and Merck (to P.K.S.) and from the Wellcome Trust and the Cancer Research Campaign (to J.R.S.), and by a Cancer Research Campaign Senior Fellowship and a Burroughs Wellcome Career Development Award to I.S.N.

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  1. Kenneth B. Kaplan

    Present address: Section of Molecular and Cellular Biology, University of California Davis, Davis, California, 95616, USA

Authors and Affiliations

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Kenneth B. Kaplan, Aurora A. Burds & Peter K. Sorger

  2. School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK

    Jason R. Swedlow, Songül S. Bekir & Inke S. Näthke

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  1. Kenneth B. Kaplan
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Correspondence to Inke S. Näthke.

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Kaplan, K., Burds, A., Swedlow, J. et al. A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat Cell Biol 3, 429–432 (2001). https://doi.org/10.1038/35070123

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