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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line
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Cytoskeletal Proteins / metabolism
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Cytoskeletal Proteins / physiology*
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Ectodermal Dysplasia / genetics
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Ectodermal Dysplasia / metabolism*
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Edar Receptor
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Genes, Reporter
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Genetic Vectors
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Humans
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I-kappa B Kinase
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Luciferases / metabolism
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Lymphoid Enhancer-Binding Factor 1
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Mice
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NF-kappa B / metabolism
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NF-kappa B / physiology*
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NF-kappaB-Inducing Kinase
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Receptors, Ectodysplasin
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Signal Transduction / physiology
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Trans-Activators / metabolism
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Trans-Activators / physiology*
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcriptional Activation / physiology*
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Transfection
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beta Catenin
Substances
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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DNA-Binding Proteins
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EDAR protein, human
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Edar Receptor
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Edar protein, mouse
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LEF1 protein, human
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Lef1 protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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Membrane Proteins
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NF-kappa B
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Receptors, Ectodysplasin
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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Trans-Activators
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Transcription Factors
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beta Catenin
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Luciferases
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Protein Serine-Threonine Kinases
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CHUK protein, human
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Chuk protein, mouse
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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Ikbkb protein, mouse
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Ikbke protein, mouse