Identification of a link between the tumour suppressor APC and the kinesin superfamily

Nature Cell Biology
Takeshi JimboTetsu Akiyama

Abstract

The tumour suppressor gene adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumours. APC is involved in the proteasome-mediated degradation of beta-catenin, through its interaction with beta-catenin, GSK-3 beta and Axin. APC also interacts with the microtubule cytoskeleton and has been localized to clusters near the distal ends of microtubules at the edges of migrating epithelial cells. Moreover, in Xenopus laevis epithelial cells, APC has been shown to move along microtubules and accumulate at their growing plus ends. However, the mechanism of APC accumulation and the nature of these APC clusters remain unknown. We show here that APC interacts with the kinesin superfamily (KIF) 3A-KIF3B proteins, microtubule plus-end-directed motor proteins, through an association with the kinesin superfamily-associated protein 3 (KAP3). The interaction of APC with KAP3 was required for its accumulation in clusters, and mutant APCs derived from cancer cells were unable to accumulate efficiently in clusters. These results suggest that APC and beta-catenin are transported along microtubules by KAP3-KIF3A-KIF3B, accumulate in the tips of membrane protrusions, and may thus regulate cell migration.

References

Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·H YamazakiN Hirokawa
Oct 18, 1996·Cell·K W Kinzler, B Vogelstein
Oct 25, 1996·The Journal of Biological Chemistry·K ShimizuY Takai
Jun 7, 1997·Biochimica Et Biophysica Acta·P Polakis
Jan 20, 1999·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·S ShibamotoS Takada
Oct 6, 1999·Current Opinion in Genetics & Development·M Bienz
Apr 27, 2000·Nature Cell Biology·B M McCartney, M Peifer
Jun 9, 2000·Annual Review of Neuroscience·L S Goldstein, Z Yang
Nov 1, 2000·Cell·M Bienz, H Clevers
Nov 21, 2000·Current Opinion in Neurobiology·S Terada, N Hirokawa
Jan 4, 2001·Cell·T A GrahamW Xu
Jul 17, 2001·EMBO Reports·A TigheS S Taylor

❮ Previous
Next ❯

Citations

Sep 5, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Angela I M Barth, W James Nelson
Oct 17, 2002·Journal of Biosciences·Ritu Sarpal, Krishanu Ray
Jun 19, 2007·Medical Molecular Morphology·Takao SendaAtsushi Shimomura
Oct 25, 2012·Journal of Molecular Neuroscience : MN·Xiaowei YuFeng Zhang
Apr 23, 2004·Trends in Biochemical Sciences·Richard S Jope, Gail V W Johnson
Jan 9, 2003·Current Opinion in Cell Biology·N Ronald Morris
Jan 9, 2003·Current Opinion in Cell Biology·Niels Galjart, Franck Perez
Oct 2, 2003·Current Opinion in Cell Biology·Masaki FukataKozo Kaibuchi
May 14, 2003·Trends in Cell Biology·Pedro CarvalhoDavid Pellman
Aug 30, 2003·Trends in Cell Biology·Juliet C Coates
Apr 15, 2009·Cell Research·Shih-Lei LaiRandall T Moon
May 14, 2005·Nature Cell Biology·Amy Reilein, W James Nelson
Apr 19, 2005·Nature Cell Biology·Junlin TengNobutaka Hirokawa
Feb 19, 2013·Nature Cell Biology·Zoltan MaligaAnthony A Hyman
Mar 7, 2008·Nature Reviews. Molecular Cell Biology·Anna Akhmanova, Michel O Steinmetz
Dec 5, 2006·Oncogene·T Akiyama, Y Kawasaki
Jun 16, 2009·The Journal of Biological Chemistry·Yoshihiro KawasakiTetsu Akiyama
Nov 10, 2009·The Journal of Biological Chemistry·Yoshihiro KawasakiTetsu Akiyama
Jul 21, 2005·Molecular Biology of the Cell·Rebecca A GreenKenneth B Kaplan
Sep 12, 2002·EMBO Reports·Beric R Henderson, Francois Fagotto
Nov 7, 2009·Development, Growth & Differentiation·Tong SunLeung Kim
Sep 15, 2005·Anatomical Science International·Takao SendaAkiko Iizuka-Kogo
Mar 25, 2010·Biochemistry. Biokhimii︠a︡·A Yu Lomakin, E S Nadezhdina
Jun 12, 2013·Annual Review of Cell and Developmental Biology·Jonathan M Scholey
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Inke S Näthke
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Yixian Zheng
Apr 9, 2005·BMC Cell Biology·Nick P RiessEwan E Morrison
Jan 21, 2006·BMC Cell Biology·Kelly J LangfordEwan E Morrison

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.