MFB-1, an F-box-type ubiquitin ligase, regulates TGF-β signalling

Authors

  • Yukako Aoyama,

    1. Department of Molecular Cell Biology, Medical Research Institute, School of Biomedical Science and CREST, Japan Science and Technology Corporation, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
    2. Maxillofacial Surgery, Postgraduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan
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  • Seiichi Urushiyama,

    1. Department of Molecular Cell Biology, Medical Research Institute, School of Biomedical Science and CREST, Japan Science and Technology Corporation, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
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  • Misato Yamada,

    1. Department of Molecular Cell Biology, Medical Research Institute, School of Biomedical Science and CREST, Japan Science and Technology Corporation, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
    2. Center of Excellence Program for Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
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  • Chikako Kato,

    1. Department of Molecular Cell Biology, Medical Research Institute, School of Biomedical Science and CREST, Japan Science and Technology Corporation, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
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  • Hiroko Ide,

    1. Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan
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  • Satoshi Higuchi,

    1. Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan
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  • Tetsu Akiyama,

    1. Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan
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  • Hiroshi Shibuya

    Corresponding author
    1. Department of Molecular Cell Biology, Medical Research Institute, School of Biomedical Science and CREST, Japan Science and Technology Corporation, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
    2. Center of Excellence Program for Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
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  • Communicated by: Eisuke Nishida

* Correspondence: E-mail: shibuya.mcb@mri.tmd.ac.jp

Abstract

TGF-β signalling regulates cell growth, differentiation, morphogenesis and apoptosis. MAFbx/Atrogin-1 has been identified as a regulator for skeletal muscle atrophy and encodes an F-box-type E3 ubiquitin ligase. However, little is known about how MAFbx/Atrogin-1 regulates cellular signalling. Here, we identify and genetically characterize MFB-1, a MAFbx/Atrogin-1 homologue from Caenorhabditis elegans. The mfb-1 deletion mutant significantly enhanced the dauer constitutive (Daf-c) phenotype caused by mutations in the DAF-7/TGF-β-like signalling pathway, but not the DAF-2/insulin receptor-like signalling pathway. Conversely, the Daf-c phenotypes of DAF-7 pathway mutants were partially suppressed by mfb-1 cDNA transgenes. Therefore, MFB-1 acts genetically downstream in the DAF-7 pathway. A mfb-1::GFP fusion was found to be expressed in the nervous system, hypodermis and intestine and overlapped expression of many DAF-7 pathway genes. We propose that MFB-1 is a novel F-box protein that negatively regulates dauer formation in concert with the DAF-7 signalling pathway in C. elegans.

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