Science · 1998 · 1.3K citations · 22 references
Life SciencesCell BiologyMolecular BiologyCell SignalingMolecular Cell BiologySignal TransductionDevelopmental Signaling PathwaysWnt SignalingApc InactivationAxin FunctionBeta-catenin RegulationCanonical Wnt PathwayMacromolecular Complex FormationWnt In Axis PatterningWnt Signaling In Axis Formation
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.
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.
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