MFB-1, an F-box-type ubiquitin ligase, regulates TGF-beta signalling.
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.
Aoyama
Yukako
Y
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.
Urushiyama
Seiichi
S
Yamada
Misato
M
Kato
Chikako
C
Ide
Hiroko
H
Higuchi
Satoshi
S
Akiyama
Tetsu
T
Shibuya
Hiroshi
H
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*
D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D016212:Transforming Growth Factor beta; D044767:Ubiquitin-Protein Ligases