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Pygopus Activates Wingless Target Gene Transcription Through the Mediator Complex Subunits Med12 and Med13

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Specialty Science
Date 2008 May 3
PMID 18451032
Citations 79
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Abstract

Wnt target gene transcription is mediated by nuclear translocation of stabilized beta-catenin, which binds to TCF and recruits Pygopus, a cofactor with an unknown mechanism of action. The mediator complex is essential for the transcription of RNA polymerase II-dependent genes; it associates with an accessory subcomplex consisting of the Med12, Med13, Cdk8, and Cyclin C subunits. We show here that the Med12 and Med13 subunits of the Drosophila mediator complex, encoded by kohtalo and skuld, are essential for the transcription of Wingless target genes. kohtalo and skuld act downstream of beta-catenin stabilization both in vivo and in cell culture. They are required for transcriptional activation by the N-terminal domain of Pygopus, and their physical interaction with Pygopus depends on this domain. We propose that Pygopus promotes Wnt target gene transcription by recruiting the mediator complex through interactions with Med12 and Med13.

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References
1.
Song W, Treich I, Qian N, Kuchin S, Carlson M . SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II. Mol Cell Biol. 1996; 16(1):115-20. PMC: 230984. DOI: 10.1128/MCB.16.1.115. View

2.
Yang F, deBeaumont R, Zhou S, Naar A . The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator. Proc Natl Acad Sci U S A. 2004; 101(8):2339-44. PMC: 356952. DOI: 10.1073/pnas.0308676100. View

3.
Neumann C, Cohen S . Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development. 1997; 124(4):871-80. DOI: 10.1242/dev.124.4.871. View

4.
Chang Y, Howard S, Herman P . The Ras/PKA signaling pathway directly targets the Srb9 protein, a component of the general RNA polymerase II transcription apparatus. Mol Cell. 2004; 15(1):107-16. DOI: 10.1016/j.molcel.2004.05.021. View

5.
Stadeli R, Basler K . Dissecting nuclear Wingless signalling: recruitment of the transcriptional co-activator Pygopus by a chain of adaptor proteins. Mech Dev. 2005; 122(11):1171-82. DOI: 10.1016/j.mod.2005.07.004. View