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MFB‐1, an F‐box‐type ubiquitin ligase, regulates TGF‐β signalling
Author(s) -
Aoyama Yukako,
Urushiyama Seiichi,
Yamada Misato,
Kato Chikako,
Ide Hiroko,
Higuchi Satoshi,
Akiyama Tetsu,
Shibuya Hiroshi
Publication year - 2004
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2004.00792.x
Subject(s) - biology , ubiquitin ligase , microbiology and biotechnology , mutant , signal transduction , f box protein , caenorhabditis elegans , hedgehog signaling pathway , phenotype , ubiquitin , gene , genetics
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 .