Elsevier

Experimental Cell Research

Volume 264, Issue 1, 10 March 2001, Pages 126-134
Experimental Cell Research

Regular Article
The Many Faces of the Tumor Suppressor Gene APC

https://doi.org/10.1006/excr.2000.5142Get rights and content

Abstract

Inactivation of the tumor suppressor adenomatous polyposis coli (APC) protein is a critical early step in the development of familial and sporadic colon cancer. Close examination of the function of APC has shown that it is a multifunctional protein involved in a wide variety of processes, including regulation of cell proliferation, cell migration, cell adhesion, cytoskeletal reorganization, and chromosomal stability. Tantalizing clues to the different functions of APC have been provided by the identification of proteins interacting with several discrete motifs within APC. Each of these putative functions could link APC inactivation with tumorigenesis. Here, we will summarize recent findings regarding the diverse role of APC. We will emphasize the interaction of APC with different binding partners, the role of these complex interactions for normal functioning of the cell, and how disruption of these interactions may play a role in tumor development. The rapid progress made recently shows the many faces of APC, leading to a constant reappreciation of this multitasking tumor suppressor protein.

References (85)

  • L. Zeng et al.

    The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation

    Cell

    (1997)
  • Y. Marikawa et al.

    beta-TrCP is a negative regulator of Wnt/beta-catenin signaling pathway and dorsal axis formation in Xenopus embryos

    Mech. Dev.

    (1998)
  • M. Boutros et al.

    Dishevelled: At the crossroads of divergent intracellular signaling pathways

    Mech. Dev.

    (1999)
  • C. Yost et al.

    GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis

    Cell

    (1998)
  • F. Fagotto et al.

    Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin

    Curr. Biol.

    (1998)
  • M. Molenaar et al.

    XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos

    Cell

    (1996)
  • R. Nusse et al.

    Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome

    Cell

    (1982)
  • J. Roose et al.

    TCF transcription factors: Molecular switches in carcinogenesis

    Biochem. Biophys. Acta

    (1999)
  • K.W. Kinzler et al.

    Identification of FAP locus genes from chromosome 5q21

    Science

    (1991)
  • I. Nishisho et al.

    Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients

    Science

    (1991)
  • Soussi: APC mutation database. Available at,...
  • Y. Miyoshi et al.

    Somatic mutations of the APC gene in colorectal tumors: Mutation cluster region in the APC gene

    Hum. Mol. Genet.

    (1992)
  • R. Fodde et al.

    Genotype–phenotype correlations at the adenomatous polyposis coli (APC) gene

    Crit. Rev. Oncogen.

    (1995)
  • L.-K. Su et al.

    Multiple intestinal neolasia caused by a mutation in the murine homolog of the APC gene

    Science

    (1992)
  • C.A. Midgley et al.

    APC expression in normal human tissues

    J. Pathol.

    (1997)
  • L.K. Su et al.

    Association between wild type and mutant APC gene products

    Cancer Res.

    (1993)
  • M. Oshima et al.

    Evidence against dominant negative mechanisms of intestinal polyp formation by APC gene mutations

    Cancer Res.

    (1995)
  • M. Hatzfeld

    The armadillo family of structural proteins

    Int. Rev. Cytol.

    (1999)
  • J.M. Seeling et al.

    Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A

    Science

    (1999)
  • Y. Kawasaki et al.

    Asef, a link between the tumor suppressor APC and G-protein signaling

    Science

    (2000)
  • L.-K. Su et al.

    Association of the APC tumor suppressor protein with catenins

    Science

    (1993)
  • B. Rubinfeld et al.

    Association of the APC gene product with catenin

    Science

    (1993)
  • B. Rubinfeld et al.

    Binding of GSK3 to the APC–beta-catenin complex and regulation of complex assembly

    Science

    (1996)
  • J. Behrens et al.

    Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3

    Science

    (1998)
  • S. Munemitsu et al.

    The APC gene product associates with microtubules in vivo and promotes their assembly in vitro

    Cancer Res.

    (1994)
  • K.J. Smith et al.

    Wild-type but not mutant APC associates with the microtubule cytoskeleton

    Cancer Res.

    (1994)
  • L.K. Su et al.

    APC binds to the novel protein EB1

    Cancer Res.

    (1995)
  • A. Matsumine et al.

    Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein

    Science

    (1996)
  • K.S. Erdmann et al.

    The adenomatous polyposis coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via analternatively spliced PDZ domain

    Oncogene

    (2000)
  • R. Smits et al.

    Apc1638T: A mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development

    Genes Dev.

    (1999)
  • K.L. Neufeld et al.

    Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm

    Proc. Natl. Acad. Sci. USA

    (2000)
  • B.R. Henderson

    Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover

    Nature Cell Biol.

    (2000)
  • Cited by (0)

    1

    To whom reprint requests should be addressed. Fax: 31 30 2517107. E-mail: [email protected].

    View full text