Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3β

TLDR

Beta‑catenin stability regulation is central to Wnt signaling. Conductin binds β‑catenin and APC, drives β‑catenin degradation, and its loss stabilizes β‑catenin; APC fragments that bind conductin block degradation, and conductin disrupts Wnt‑induced axis formation in Xenopus embryos.

Abstract

Control of stability of beta-catenin is central in the wnt signaling pathway. Here, the protein conductin was found to form a complex with both beta-catenin and the tumor suppressor gene product adenomatous polyposis coli (APC). Conductin induced beta-catenin degradation, whereas mutants of conductin that were deficient in complex formation stabilized beta-catenin. Fragments of APC that contained a conductin-binding domain also blocked beta-catenin degradation. Thus, conductin is a component of the multiprotein complex that directs beta-catenin to degradation and is located downstream of APC. In Xenopus embryos, conductin interfered with wnt-induced axis formation.