FIGURE 6.

Schematic depicting modes of action of Jade-1S relevant to β-catenin ubiquitination. The plant homeodomain zinc finger protein Jade-1 can act as an E3 ubiquitin ligase for β-catenin in both the nucleus and the cytosol, as described by Chitalia et al. (26). NPHP4 stabilizes a non-phosphorylated form of Jade-1 and enhances translocation of Jade-1 to the nucleus, promoting the ability of Jade-1 to inhibit canonical Wnt signaling, as described by Borgal et al. (27). Our data demonstrate that CK1α is able to phosphorylate Jade-1 at a conserved SLS residue and that this phosphorylation abrogates the ability of Jade-1 to inhibit β-catenin signaling. Phosphorylation (P) of Jade-1 by CK1 most likely affects nuclear Jade-1 and could abrogate activity by limiting the ability of Jade-1 to ubiquitinate (Ub) β-catenin.