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

-Catenin, an integral part of cadherin-catenin adhesion complexes, is a major binding partner of -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 -catenin fraction, we investigated the role of -catenin family members in -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 -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 -catenin signals, and the synergy between Ras and -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, -catenin and Ras signals converging on the cyclin D1 promoter.