The ectodermal dysplasia receptor represses the Lef-1/beta-catenin-dependent transcription independent of NF-kappaB activation

Biochem Biophys Res Commun. 2004 Feb 27;315(1):73-8. doi: 10.1016/j.bbrc.2004.01.025.

Abstract

EDAR plays a key role in the process of ectodermal differentiation via activation of the NF-kappaB pathway. We present evidence that EDAR also represses Lef-1/beta-catenin-dependent transcription and this ability is defective in EDAR mutants associated with anhidrotic ectodermal dysplasia. While IKK1/IKKalpha and IKK2/IKKbeta are required for EDAR-induced NF-kappaB activation, they are dispensable for its ability to repress Lef-1/beta-catenin-dependent transcription. In contrast, NIK is not involved in EDAR-induced NF-kappaB activation or Lef-1/beta-catenin transcriptional repression. As Lef-1/beta-catenin pathway controls the expression of EDAR ligand, ectodysplasin-A (EDA), our results point to a negative feedback regulation of EDA-EDAR axis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Ectodermal Dysplasia / genetics
  • Ectodermal Dysplasia / metabolism*
  • Edar Receptor
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • I-kappa B Kinase
  • Luciferases / metabolism
  • Lymphoid Enhancer-Binding Factor 1
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • NF-kappaB-Inducing Kinase
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Receptors, Ectodysplasin
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction / physiology
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcriptional Activation / physiology*
  • Transfection
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • EDAR protein, human
  • Edar Receptor
  • Edar protein, mouse
  • LEF1 protein, human
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Ectodysplasin
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Trans-Activators
  • Transcription Factors
  • beta Catenin
  • Luciferases
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • Chuk protein, mouse
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Ikbkb protein, mouse
  • Ikbke protein, mouse