Frat oncoproteins act at the crossroad of canonical and noncanonical Wnt-signaling pathways
| Autor: | Anton Berns, Natalie Proost, R. van Amerongen, J-P Lambooij, Jos Jonkers, Martijn C. Nawijn |
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| Přispěvatelé: | Groningen Research Institute for Asthma and COPD (GRIAC) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Cancer Research Frizzled lymphoma-genesis Dishevelled Proteins VERTEBRATES planar cell polarity BETA-CATENIN Glycogen Synthase Kinase 3 Mice Diversin GSK-3 AXIN Drosophila Proteins Frat Gsk3-binding protein PHOSPHORYLATION beta Catenin Tissue homeostasis Mice Knockout chemistry.chemical_classification Intracellular Signaling Peptides and Proteins Wnt signaling pathway LRP6 GLYCOGEN-SYNTHASE KINASE-3 Neoplasm Proteins Dishevelled Female GASTRULATION TCF Transcription Factors Signal Transduction Beta-catenin Cellular polarity CELL POLARITY Blotting Western Biology Lymphoma T-Cell Transfection Cell Line Proto-Oncogene Proteins Wnt-signal transduction Genetics Animals Humans KINASE-I-EPSILON Molecular Biology Adaptor Proteins Signal Transducing Glycogen Synthase Kinase 3 beta JNK Mitogen-Activated Protein Kinases NEURAL-TUBE CLOSURE Phosphoproteins Survival Analysis Mice Inbred C57BL Transcription Factor AP-1 Wnt Proteins Cytoskeletal Proteins chemistry PLANAR POLARITY Cancer research biology.protein Carrier Proteins |
| Zdroj: | ONCOGENE, 29(1), 93-104. Nature Publishing Group |
| ISSN: | 0950-9232 |
| DOI: | 10.1038/onc.2009.310 |
| Popis: | Wnt-signal transduction is critical for development and tissue homeostasis in a wide range of animal species and is frequently deregulated in human cancers. Members of the Frat/GBP family of glycogen synthase kinase 3 beta (Gsk3b)binding oncoproteins are recognized as potent activators of the Wnt/beta-catenin pathway in vertebrates. Here, we reveal a novel, Gsk3b-independent function of Frat converging on the activation of JNK and AP-1. Both these have been used as readouts for the noncanonical Frizzled/PCP pathway, which controls polarized cell movements and the establishment of tissue polarity. We find that Frat synergizes with Diversin, the mammalian homolog of the Drosophila PCP protein diego, in the activation of JNK/AP-1 signaling. Importantly, Frat mutants deficient for binding to Gsk3b retain oncogenic activity in vivo, suggesting that Wnt/beta-catenin-independent events contribute to Frat-induced malignant transformation. The observed activities of Frat are reminiscent of the dual function of Dishevelled in the Wnt/beta-catenin and Frizzled/PCP pathways and suggest that Frat may also function to bridge canonical and noncanonical Wnt pathways. |
| Databáze: | OpenAIRE |
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