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Molecular and Cellular Biology, March 2004, p. 2410-2422, Vol. 24, No. 6
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.6.2410-2422.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Distinct Activities of the -Catenin Family, -Catulin and -Catenin, on ß-Catenin-Mediated Signaling

Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111

Received 3 September 2003/ Returned for modification 7 October 2003/ Accepted 17 December 2003

-Catenin, an integral part of cadherin-catenin adhesion complexes, is a major binding partner of ß-catenin, a key component of the Wnt pathway, which activates T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription and is often upregulated in cancers. Recently, we identified an -catenin-related protein, -catulin, whose function is poorly understood, as part of a Rho GTPase signaling complex. Here, based on evidence suggesting that -catulin may associate with a ß-catenin fraction, we investigated the role of -catenin family members in ß-catenin-mediated signals. Expression of the full length or a 103-residue region of -catenin strongly inhibits the induction of the TCF/LEF-responsive TOPFLASH reporter in HEK293T cells expressing activated ß-catenin or in cancer cells with constitutively upregulated Wnt signaling, whereas -catulin expression had no effect. Interestingly, -catulin expression attenuates the activation of the cyclin D1 promoter, a target of Wnt pathway signals. -Catulin appears to inhibit Ras-mediated signals to the cyclin D1 promoter, rather than ß-catenin signals, and the synergy between Ras and ß-catenin required to fully activate this promoter. Data suggesting the involvement of Rho in this response are presented and discussed. These results suggest a novel function for -catulin and imply that -catenin and -catulin have distinct activities that downregulate, respectively, ß-catenin and Ras signals converging on the cyclin D1 promoter.

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