Identification and characterization of Xenopus laevis homologs of mammalian TRAF6 and its binding protein TIFA

Gene. 2005 Sep 26;358:53-9. doi: 10.1016/j.gene.2005.05.016.


Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) transduces signals from members of the TNFR superfamily and the Toll/IL-1R family, leading to activation of transcription factors such as NFkappaB and AP-1. Genetic disruption of the TRAF6 gene in mice results in various developmental abnormalities during embryogenesis, including osteopetrosis, failure of neural tube closure, defective formation of skin appendices, absence of lymph nodes, and absence of mature thymic epithelial cells. To clarify the effect of TRAF6 in development, we previously identified a TRAF-interacting protein with a forkhead-associated domain (TIFA), which binds and activates TRAF6 upon extracellular stimulation. To understand the physiological roles of TRAF6 and TIFA in early development, we studied these genes in Xenopus laevis. Here, we describe identification of X. laevis homologs of mammalian TRAF6 (XTRAF6) and TIFA (XTIFA). As was the case for the mammalian homologs, overexpression of XTRAF6 or XTIFA activated NFkappaB, whereas XTIFA carrying a mutation that abolishes XTRAF6 binding failed to activate NFkappaB, suggesting that XTIFA activates NFkappaB by binding to XTRAF6. XTIFA and XTRAF6 mRNAs were expressed at similar levels in zygotes from the neurula stage and then increased. Whole-mount in situ hybridization revealed that XTRAF6 mRNA was expressed in the head region and neural tube during the neurula stage, and the expression expanded to the pharyngeal apparatus during the tailbud stage. This localization is consistent with the defective neural tube closure and abnormal thymus organogenesis observed in TRAF6-deficient mice. Our results suggest possible cooperation between XTRAF6 and XTIFA during embryogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation, Developmental / physiology*
  • Humans
  • Lymph Nodes / embryology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • NF-kappa B / metabolism
  • Neural Tube Defects / genetics
  • Neural Tube Defects / metabolism
  • Organogenesis / physiology*
  • Osteopetrosis / genetics
  • Osteopetrosis / metabolism
  • Pharynx / embryology
  • Protein Binding / physiology
  • Sequence Homology, Amino Acid
  • Skin Abnormalities / genetics
  • Skin Abnormalities / metabolism
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism*
  • Thymus Gland / embryology
  • Thymus Gland / pathology
  • Transcription Factor AP-1 / metabolism
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis


  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • TIFA protein, X laevis
  • TNF Receptor-Associated Factor 6
  • Transcription Factor AP-1
  • Xenopus Proteins