A role for the Adenomatous Polyposis Coli protein in chromosome segregation

Kenneth B. Kaplan, Aurora A. Burds, Jason R. Swedlow, Songül S. Bekir, Peter K. Sorger, Inke S. Näthke

Research output: Contribution to journalArticle

445 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)429-432
Number of pages4
JournalNature Cell Biology
Volume3
Issue number4
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Cell Biology

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    Kaplan, K. B., Burds, A. A., Swedlow, J. R., Bekir, S. S., Sorger, P. K., & Näthke, I. S. (2001). A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nature Cell Biology, 3(4), 429-432. https://doi.org/10.1038/35070123