Zinc Finger, BED Type Containing Protein 3 (ZBED3)

Zbed3 contains a PPPPSPT motif, which is crucial to its binding to Axin. The Ser and Thr residues in the motif appear to be also phosphorylated by glycogen synthase kinase 3β (GSK3β) and the CKI family kinases, as GSK3β and CKIϵ could enhance the interaction of Zbed3 with Axin. Expressing Zbed3, but not these mutants, led to inhibition of GSK3β-mediated β-catenin phosphorylation, cytoplasmic β-catenin accumulation, and activation of lymphoid enhancer binding factor-1-dependent reporter gene transcription. Furthermore, knockdown of Zbed3 with RNA interference attenuated Wnt-induced β-catenin accumulation, lymphoid enhancer binding factor-1-dependent luciferase reporter activity, and the Wnt target gene expression. Zbed3 is a novel Axin-binding protein that is involved in Wnt/β-catenin signaling modulation.