RNA Helicase DDX3 Is a Regulatory Subunit of Casein Kinase 1 in Wnt/β-Catenin Signaling

Casein kinase 1 (CK1) members play key roles in numerous biological processes. They are considered “rogue” kinases, since their enzymatic activity appears unregulated. Contrary to this notion, we have identified the DEAD box RNA helicase DDX3 as a novel regulator of the Wnt/β-catenin network, where it acts as a regulatory subunit of CK1ε: In a Wnt-dependent manner, DDX3 binds CK1ε and directly stimulates its kinase activity, and promotes phosphorylation of the scaffold protein Dishevelled. DDX3 is required for Wnt/β-catenin signaling in mammalian cells, and during Xenopus- and C. elegans development. The results also suggest that the kinase-stimulatory function extends to other DDX- and CK1 members, opening fresh perspectives for one of the longest studied protein kinase families.