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Brief Report |
Correspondence to: Randall T. Moon, Room K536C Health Sciences Building, Campus Box 357750, Department of Pharmacology, University of Washington, Seattle, WA 98195. Tel:(206) 543-1722 Fax:(206) 616-4230 E-mail:rtmoon{at}u.washington.edu.
ß-Catenin plays a pivotal role in the transcriptional activation of Wnt-responsive genes by binding to TCF/LEF transcription factors. Although it has been suggested that the COOH-terminal region of ß-catenin functions as an activation domain, the mechanisms of activation remain unclear. To screen for potential transcriptional coactivators that bind to the COOH-terminal region of ß-catenin, we used a novel yeast two-hybrid system, the Ras recruitment system (RRS) that detects protein–protein interactions at the inner surface of the plasma membrane. Using this system, we isolated the CREB-binding protein (CBP). Armadillo (Arm) repeat 10 to the COOH terminus of ß-catenin is involved in binding to CBP, whereas ß-catenin interacts directly with the CREB-binding domain of CBP. ß-Catenin synergizes with CBP to stimulate the activity of a synthetic reporter in vivo. Conversely, ß-catenin–dependent transcriptional activation is repressed by E1A, an antagonist of CBP function, but not by an E1A mutant that does not bind to CBP. The activation of Wnt target genes such as siamois and Xnr3 in Xenopus embryos is also sensitive to E1A. These findings suggest that CBP provides a link between ß-catenin and the transcriptional machinery, and possibly mediates the oncogenic function of ß-catenin.
Key Words: Xenopus laevis, CREB-binding protein, T cell factor/lymphoid enhancer factor, transcriptional activation, Wnt
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