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).
Chen, YG, Ning, Y, Zhang, L, Wen, J, Gao, X
Waxman, JS, Fox, EP, Khlebtsova, N, Sheldahl, LC, Cheyette, BN, Takemaru, K, Miller, JR, Moon, RT, Earnest, T
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