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APC Proteins pp 13–29Cite as

Nuclear APC

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 656))

Abstract

Mutational inactivation of the tumor suppressor gene APC (Adenomatous polyposis coli) is thought to be an initiating step in the progression of the vast majority of colorectal cancers. Attempts to understand APC function have revealed more than a dozen binding partners as well as several subcellular localizations including at cell-cell junctions, associated with microtubules at the leading edge of migrating cells, at the apical membrane, in the cytoplasm and in the nucleus. The present chapter focuses on APC localization and functions in the nucleus. APC contains two classical nuclear localization signals, with a third domain that can enhance nuclear import. Along with two sets of nuclear export signals, the nuclear localization signals enable the large APC protein to shuttle between the nucleus and cytoplasm. Nuclear APC can oppose β-catenin-mediated transcription. This down-regulation of nuclear β-catenin activity by APC most likely involves nuclear sequestration of β-catenin from the transcription complex as well as interaction of APC with transcription corepressor CtBP. Additional nuclear binding partners for APC include transcription factor activator protein AP-2α, nuclear export factor Crm1, protein tyrosine phosphatase PTP-BL and perhaps DNA itself. Interaction of APC with polymerase β and PCNA, suggests a role for APC in DNA repair. The observation that increases in the cytoplasmic distribution of APC correlate with colon cancer progression suggests that disruption of these nuclear functions of APC plays an important role in cancer progression. APC prevalence in the cytoplasm of quiescent cells points to a potential function for nuclear APC in control of cell proliferation. Clear definition of APC’s nuclear function(s) will expand the possibilities for early colorectal cancer diagnostics and therapeutics targeted to APC.

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Authors and Affiliations

  1. Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA

    Kristi L. Neufeld

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  1. Kristi L. Neufeld
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Correspondence to Kristi L. Neufeld .

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Editors and Affiliations

  1. Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK

    Inke S. Näthke

  2. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA

    Brooke M. McCartney

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© 2009 Landes Bioscience and Springer Science+Business Media

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Neufeld, K.L. (2009). Nuclear APC. In: Näthke, I.S., McCartney, B.M. (eds) APC Proteins. Advances in Experimental Medicine and Biology, vol 656. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1145-2_2

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