HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/4/C747    most recent 00433.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Gottardi, C. J. Articles by Gumbiner, B. M. Search for Related Content PubMed PubMed Citation Articles by Gottardi, C. J. Articles by Gumbiner, B. M.

EXTRACELLULAR MATRIX, CELL INTERACTIONS

Role for ICAT in -catenin-dependent nuclear signaling and cadherin functions

Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908-0732

Submitted 7 October 2003 ; accepted in final form 11 November 2003

Inhibitor of -catenin and TCF-4 (ICAT) is a 9-kDa polypeptide that inhibits -catenin nuclear signaling by binding -catenin and competing its interaction with the transcription factor TCF (T cell factor), but basic characterization of the endogenous protein and degree to which it alters other -catenin functions is less well understood. At the subcellular level, we show that ICAT localizes to both cytoplasmic and nuclear compartments. In intestinal tissue, ICAT is upregulated in the mature, nondividing enterocyte population lining intestinal villi and is absent in the -catenin/TCF signaling-active crypt region, suggesting that its protein levels may be inversely related with -catenin signaling activity. However, ICAT protein levels are not altered by activation or inhibition of Wnt signaling in cultured cells, suggesting that ICAT expression is not a direct target of the Wnt/-catenin pathway. In cells where -catenin levels are elevated by Wnt, a fraction of this -catenin pool is associated with ICAT, suggesting that ICAT may buffer the cell from increased levels of -catenin. Distinct from TCF and cadherin, ICAT does not protect the soluble pool of -catenin from degradation by the adenomatous polyposis coli containing "destruction complex." Although ICAT inhibits -catenin binding to the cadherin as well as TCF in vitro, stable overexpression of ICAT in Madin-Darby canine kidney (MDCK) epithelial cells shows no obvious alterations in the cadherin complex, suggesting that the ability of ICAT to inhibit -catenin binding to the cadherin may be restricted in vivo. MDCK cells overexpressing ICAT do, however, exhibit enhanced cell scattering on hepatocyte growth factor treatment, suggesting a possible role in the regulation of dynamic rather than steady-state cell-cell adhesions. These findings confirm ICAT's primary role in -catenin signaling inhibition and further suggest that ICAT may have consequences for cadherin-based adhesive function in certain circumstances, implying a broader role than previously described.

cadherin-mediated cell-cell adhesion; Wnt/-catenin signaling

This article has been cited by other articles:

				J. Arikkath, I. Israely, Y. Tao, L. Mei, X. Liu, and L. F. Reichardt Erbin Controls Dendritic Morphogenesis by Regulating Localization of {delta}-Catenin J. Neurosci., July 9, 2008; 28(28): 7047 - 7056. [Abstract] [Full Text] [PDF]

				M. Z. Hossain, Q. Yu, M. Xu, and J. M. Sen ICAT expression disrupts {beta}-catenin-TCF interactions and impairs survival of thymocytes and activated mature T cells Int. Immunol., July 1, 2008; 20(7): 925 - 935. [Abstract] [Full Text] [PDF]

				M. Guo, J. W. Breslin, M. H. Wu, C. J. Gottardi, and S. Y. Yuan VE-cadherin and {beta}-catenin binding dynamics during histamine-induced endothelial hyperpermeability Am J Physiol Cell Physiol, April 1, 2008; 294(4): C977 - C984. [Abstract] [Full Text] [PDF]

				J. L. Herington, J. Bi, J. D. Martin, and B. M. Bany {beta}-Catenin (CTNNB1) in the Mouse Uterus During Decidualization and the Potential Role of Two Pathways in Regulating Its Degradation J. Histochem. Cytochem., September 1, 2007; 55(9): 963 - 974. [Abstract] [Full Text] [PDF]

				A. Strom, C. Bonal, R. Ashery-Padan, N. Hashimoto, M. L. Campos, A. Trumpp, T. Noda, Y. Kido, F. X. Real, F. Thorel, et al. Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas Development, August 1, 2007; 134(15): 2719 - 2725. [Abstract] [Full Text] [PDF]

				F.-S. Chou, P.-S. Wang, S. Kulp, and J. J. Pinzone Effects of Thiazolidinediones on Differentiation, Proliferation, and Apoptosis Mol. Cancer Res., June 1, 2007; 5(6): 523 - 530. [Abstract] [Full Text] [PDF]

				C. J. Gottardi and B. M. Gumbiner Distinct molecular forms of {beta}-catenin are targeted to adhesive or transcriptional complexes J. Cell Biol., October 25, 2004; 167(2): 339 - 349. [Abstract] [Full Text] [PDF]

				J. L. Stow ICAT is a multipotent inhibitor of {beta}-catenin. Focus on "Role for ICAT in {beta}-catenin-dependent nuclear signaling and cadherin functions" Am J Physiol Cell Physiol, April 1, 2004; 286(4): C745 - C746. [Full Text] [PDF]