Anatomical Science International

, Volume 80, Issue 3, pp 121–131

Adenomatous polyposis coli (Apc) tumor suppressor gene as a multifunctional gene

  • Takao Senda
  • Atsushi Shimomura
  • Akiko Iizuka-Kogo
Review Article

DOI: 10.1111/j.1447-073x.2005.00106.x

Cite this article as:
Senda, T., Shimomura, A. & Iizuka-Kogo, A. Anato Sci Int (2005) 80: 121. doi:10.1111/j.1447-073x.2005.00106.x

Abstract

The adenomatous polyposis coli (Apc) gene is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. The Apc gene product (APC), basically a cytoplasmic protein, blocks cell cycle progression and plays crucial roles in development. The APC binds to β-catenin, axin and glycogen synthase kinase 3β to form a large protein complex, in which β-catenin is phosphorylated and broken down, resulting in negative regulation of the Wnt signaling pathway. Most of the mutated Apc genes in colorectal tumors lack β-catenin-binding regions and fail to inhibit Wnt signaling, leading to overproliferation of tumor cells. The APC, having some nuclear localizing signals in its molecule, can also be localized in the nucleus. The nuclear APC exports excess β-catenin to the cytoplasm. Through its C-terminus, APC binds to post-synaptic density discs large zonula occludens domain-containing proteins, such as discs large (DLG) and post-synaptic density (PSD)-95, and may play important roles in epithelial morphogenesis, brain development and neuronal functions. In addition, APC is involved in cell motility through its association with microtubules and APC-stimulated guanine nucleotide exchange factor. Colocalization of APC and DLG is dependent on microtubules. The Apc gene is highly expressed in the embryonic and postnatal developing brain. Recently, we found that APC is required for the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by facilitating the clustering of PSD-95 and these receptors at the postsynapse. In addition, APC is present in astrocytes, although its role in astrocytes is, as yet, unknown.

Key words

adenomatous polyposis coli (Apc) geneβ-cateninsynapsetumor suppressorWnt signaling

Copyright information

© Japanese Association of Anatomists 2005

Authors and Affiliations

  • Takao Senda
    • 1
  • Atsushi Shimomura
    • 1
  • Akiko Iizuka-Kogo
    • 1
  1. 1.Department of Anatomy IFujita Health University School of MedicineToyoake AichiJapan