Inhibition of nuclear factor-kappaB-mediated transcription by association with the amino-terminal enhancer of split, a Groucho-related protein lacking WD40 repeats.
The amino-terminal enhancer of split (AES) encodes a 197-amino acid protein that is homologous to the NH(2)-terminal domain of the Drosophila Groucho protein but lacks COOH-terminal WD40 repeats. Although the Drosophila Groucho protein and its mammalian homologs, transducin-like enhancer of split proteins, are known to act as non-DNA binding corepressors, ... the role of the AES protein remains unclarified. Using the yeast two-hybrid system, we have identified the protein-protein interaction between AES and the p65 (RelA) subunit of the transcription factor nuclear factor kappaB (NF-kappaB), which activates various target genes involved in inflammation, apoptosis, and embryonic development. The interaction between AES and p65 was confirmed by in vitro glutathione S-transferase pull down assay and by in vivo co-immunoprecipitation study. In transient transfection assays, AES repressed p65-driven gene expression. AES also inhibited NF-kappaB-dependent gene expression induced by tumor necrosis factor alpha, interleukin-1beta, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1, which is an upstream kinase for NF-kappaB activation. These data indicate that AES acts as a corepressor for NF-kappaB and suggest that AES may play a pivotal role in the regulation of NF-kappaB target genes.
Mesh Terms:
Basic Helix-Loop-Helix Transcription Factors, DNA-Binding Proteins, Gene Expression Regulation, Genes, Reporter, Glutathione Transferase, HIV-1, Helminth Proteins, Humans, Interleukin-1, Interleukin-6, Jurkat Cells, MAP Kinase Kinase Kinase 1, NF-kappa B, Precipitin Tests, Protein-Serine-Threonine Kinases, Proteins, Repressor Proteins, Transcription Factor RelA, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha, Yeasts
Basic Helix-Loop-Helix Transcription Factors, DNA-Binding Proteins, Gene Expression Regulation, Genes, Reporter, Glutathione Transferase, HIV-1, Helminth Proteins, Humans, Interleukin-1, Interleukin-6, Jurkat Cells, MAP Kinase Kinase Kinase 1, NF-kappa B, Precipitin Tests, Protein-Serine-Threonine Kinases, Proteins, Repressor Proteins, Transcription Factor RelA, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha, Yeasts
J. Biol. Chem.
Date: Feb. 11, 2000
PubMed ID: 10660609
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