DACT1, also known as DAPPER1, was identified in Xenopus as a negative regulator of WNT canonical and non-canonical signaling. In Xenopus, DACT1 has been shown to form a complex with GSK3beta, AXIN, CSNK1 and beta-catenin when co-expressed in HEK293 cells with DVL, and expression of DACT1 negatively regulates expression of beta-catenin target genes (Cheyette et al, 2002). In human cells, DACT1 co-precipitates with DVL2, an interaction mediated by the DIX domain of DVL2 and the C-terminal region of DACT1. siRNA depletion of DACT1 results in higher expression of beta-catenin dependent reporters and increased protein levels of DVL2, suggesting that DACT1 restricts beta-catenin-dependent signaling by promoting the degradation of DVL2. Consistent with this, lysosome inhibitors block DACT1-induced degradation of DVL2 (Zhang et al, 2006).
Cheyette, BN, Waxman, JS, Miller, JR, Takemaru, K, Sheldahl, LC, Khlebtsova, N, Fox, EP, Earnest, T, Moon, RT
Zhang, L, Gao, X, Wen, J, Ning, Y, Chen, YG
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