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    Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization.

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    Authors
    Kagermeier-Schenk, B
    Wehner, D
    Ozhan-Kizil, G
    Yamamoto, H
    Li, J
    Kirchner, K
    Hoffmann, C
    Stern, Peter L
    Kikuchi, A
    Schambony, A
    Weidinger, G
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    Affiliation
    Biotechnology Center and Center for Regenerative Therapies, Technische Universität Dresden, Tatzberg 47, 01307 Dresden, Germany.
    Issue Date
    2011-12-13
    
    Metadata
    Show full item record
    Abstract
    Wnt proteins can activate distinct signaling pathways, but little is known about the mechanisms regulating pathway selection. Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways. Waif1 inhibits β-catenin signaling in zebrafish and Xenopus embryos as well as in mammalian cells, and zebrafish waif1a acts as a direct feedback inhibitor of wnt8-mediated mesoderm and neuroectoderm patterning during zebrafish gastrulation. Waif1a binds to the Wnt coreceptor LRP6 and inhibits Wnt-induced LRP6 internalization into endocytic vesicles, a process that is required for pathway activation. Thus, Waif1a modifies Wnt/β-catenin signaling by regulating LRP6 subcellular localization. In addition, Waif1a enhances β-catenin-independent Wnt signaling in zebrafish embryos and Xenopus explants by promoting a noncanonical function of Dickkopf1. These results suggest that Waif1 modulates pathway selection in Wnt-receiving cells.
    Citation
    Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. 2011, 21 (6):1129-43 Dev Cell
    Journal
    Developmental Cell
    URI
    http://hdl.handle.net/10541/227812
    DOI
    10.1016/j.devcel.2011.10.015
    PubMed ID
    22100263
    Type
    Article
    Language
    en
    ISSN
    1878-1551
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.devcel.2011.10.015
    Scopus Count
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    All Paterson Institute for Cancer Research

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