title: MFB-1, an F-box-type ubiquitin ligase, regulates TGF-beta signalling.
abstract: TGF-beta 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-beta-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.
authors.affiliation: 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.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Seiichi
authors.initials: S
authors.lastname: Urushiyama
authors.forename: Misato
authors.initials: M
authors.lastname: Yamada
authors.forename: Chikako
authors.initials: C
authors.lastname: Kato
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ide
authors.forename: Satoshi
authors.initials: S
authors.lastname: Higuchi
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibuya
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D016212:Transforming Growth Factor beta; D044767:Ubiquitin-Protein Ligases