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

Genes Cells. 2004 Nov;9(11):1093-101. doi: 10.1111/j.1365-2443.2004.00792.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • DAF-7 protein, C elegans
  • Transforming Growth Factor beta
  • Ubiquitin-Protein Ligases