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

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2004-11, Vol.9 (11), p.1093-1101
• Main Authors: Aoyama, Yukako, Urushiyama, Seiichi, Yamada, Misato, Kato, Chikako, Ide, Hiroko, Higuchi, Satoshi, Akiyama, Tetsu, Shibuya, Hiroshi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; Hypodermis; Molecular Sequence Data; Mutation; Sequence Homology, Amino Acid; Signal Transduction; Transforming Growth Factor beta - metabolism; Ubiquitin-Protein Ligases - metabolism
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/j.1365-2443.2004.00792.x

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.