Nucleic Acids Research Advance Access originally published online on March 7, 2007
Nucleic Acids Research 2007 35(6):2084-2092; doi:10.1093/nar/gkm095
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Nucleic Acids Research, 2007, Vol. 35, No. 6 2084-2092
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Role of GAC63 in transcriptional activation mediated by ß-catenin
1Department of Pathology, 2Department of Biochemistry and Molecular Biology, and 3Division of Gastroenterology and Liver Diseases, University of Southern California, Los Angeles, California 90089, USA
*To whom correspondence should be addressed. Tel: +1-323 865 3852; Fax: +1-323 865 3866; Email: stallcup{at}usc.edu
Received October 24, 2006. Revised January 3, 2007. Accepted February 2, 2007.
ß-Catenin is a key mediator in the canonical Wnt signaling pathway, which plays important roles in multiple developmental processes. Inappropriate activation of this pathway leads to developmental defects and development of certain cancers. Upon Wnt signaling, ß-catenin binds TCF/LEF transcription factors. The TCF/LEF-ß-catenin complex then recruits a variety of transcriptional coactivators to the promoter/enhancer region of Wnt-responsive genes and activates target gene transcription. In this article, we demonstrate that GRIP1-associated coactivator 63 (GAC63), a recently identified nuclear receptor (NR) coactivator, interacts with ß-catenin. The N-terminus of GAC63 is the binding site for ß-catenin, whereas a C-terminal fragment of ß-catenin including armadillo repeats 10–12 binds to GAC63. Over-expression of GAC63 enhanced the transcriptional activity of ß-catenin, and also greatly enhanced TCF/LEF-regulated reporter gene activity in a ß-catenin-dependent manner. Endogenous GAC63 was recruited to TCF/LEF-responsive enhancer elements when ß-catenin levels were induced by LiCl. In addition, reduction of endogenous GAC63 level by small interfering RNA (siRNA) inhibited TCF/LEF-mediated gene transcription. Our findings reveal a new function of GAC63 in transcriptional activation of Wnt-responsive genes.
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