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

J. Biol. Chem., Vol. 281, Issue 20, 14066-14075, May 19, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/20/14066    most recent M602696200v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, S. Articles by Boyer, T. G. Search for Related Content PubMed PubMed Citation Articles by Kim, S. Articles by Boyer, T. G. Social Bookmarking                      What's this?

Mediator Is a Transducer of Wnt/-Catenin Signaling^*

Seokjoong Kim, Xuan Xu, Andreas Hecht, and Thomas G. Boyer¹

From the Department of Molecular Medicine and the Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245-3207 and the Institut für Molekulare Medizin und Zellforschung, Universität Freiburg, D-79104 Freiburg, Germany

Signal transduction within the canonical Wnt/-catenin pathway drives development and carcinogenesis through programmed or unprogrammed changes in gene transcription. Although the upstream events linked to signal-induced activation of -catenin in the cytoplasm have been deciphered in considerable detail, much less is known regarding the mechanism by which -catenin stimulates target gene transcription in the nucleus. Here, we show that -catenin physically and functionally targets the MED12 subunit in Mediator to activate transcription. The -catenin transactivation domain bound directly to isolated MED12 and intact Mediator both in vitro and in vivo, and Mediator was recruited to Wnt-responsive genes in a -catenin-dependent manner. Disruption of the -catenin/MED12 interaction through dominant-negative interference- or RNA interference-mediated MED12 suppression inhibited -catenin transactivation in response to Wnt signaling. This study thus identifies the MED12 interface within Mediator as a new component and a potential therapeutic target in the Wnt/-catenin pathway.

Received for publication, March 22, 2006

^* This work was supported by Career Development Award DAMD17-02-1-0584 and IDEA Award DAMD17-03-1-0272 from the United States Army Department of Defense Breast Cancer Research Program (to T. G. B.) and by United States Public Health Service Grant CA-098301 from NCI, National Institutes of Health (to T. G. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Molecular Medicine, University of Texas Health Science Center, 15355 Lambda Dr., San Antonio, TX 78245-3207. Tel.: 210-567-7258; Fax: 210-567-7247; E-mail: boyer{at}uthscsa.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Sustmann, H. Flach, H. Ebert, Q. Eastman, and R. Grosschedl Cell-Type-Specific Function of BCL9 Involves a Transcriptional Activation Domain That Synergizes with {beta}-Catenin Mol. Cell. Biol., May 15, 2008; 28(10): 3526 - 3537. [Abstract] [Full Text] [PDF]

				I. Carrera, F. Janody, N. Leeds, F. Duveau, and J. E. Treisman Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13 PNAS, May 6, 2008; 105(18): 6644 - 6649. [Abstract] [Full Text] [PDF]

				W. Xu and D. Kimelman Mechanistic insights from structural studies of beta-catenin and its binding partners J. Cell Sci., October 1, 2007; 120(19): 3337 - 3344. [Abstract] [Full Text] [PDF]

				C. E Schwartz, P. S Tarpey, H. A Lubs, A. Verloes, M. M May, H. Risheg, M. J Friez, P A. Futreal, S. Edkins, J. Teague, et al. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene J. Med. Genet., July 1, 2007; 44(7): 472 - 477. [Abstract] [Full Text] [PDF]

				R. Vijayvargia, M. S. May, and J. D. Fondell A Coregulatory Role for the Mediator Complex in Prostate Cancer Cell Proliferation and Gene Expression Cancer Res., May 1, 2007; 67(9): 4034 - 4041. [Abstract] [Full Text] [PDF]

				Y.-H. Chen, C. K. Yang, M. Xia, C.-Y. Ou, and M. R. Stallcup Role of GAC63 in transcriptional activation mediated by {beta}-catenin Nucleic Acids Res., March 19, 2007; 35(6): 2084 - 2092. [Abstract] [Full Text] [PDF]

				M. I. Reinhold and M. C. Naski Direct Interactions of Runx2 and Canonical Wnt Signaling Induce FGF18 J. Biol. Chem., February 9, 2007; 282(6): 3653 - 3663. [Abstract] [Full Text] [PDF]

				H. Zhou, S. Kim, S. Ishii, and T. G. Boyer Mediator Modulates Gli3-Dependent Sonic Hedgehog Signaling Mol. Cell. Biol., December 1, 2006; 26(23): 8667 - 8682. [Abstract] [Full Text] [PDF]

				X. Wang, N. Yang, E. Uno, R. G. Roeder, and S. Guo A subunit of the mediator complex regulates vertebrate neuronal development PNAS, November 14, 2006; 103(46): 17284 - 17289. [Abstract] [Full Text] [PDF]