Identification of a ZU5 and death domain-containing inhibitor of NF-kappaB.
The transcription factor NF-kappaB plays important roles in inflammation and cell survival. NF-kappaB is composed of homodimeric and heterodimeric complexes of Rel/NF-kappaB family members, including p65 (RelA), c-Rel (Rel), RelB, NF-kappaB1/p50, and NF-kappaB2/p52. Here we report the identification and characterization of a novel ZU5 and death domain-containing protein designated ZUD. ... In reporter gene assays, overexpression of ZUD inhibited NF-kappaB-dependent transcription induced by both tumor necrosis factor (TNF) and interleukin-1 and their downstream signaling proteins. Gel shift assays indicated that the overexpression of ZUD inhibited binding of NF-kappaB to its target sequence. ZUD is a cytoplasmic protein, and coimmunoprecipitation assays indicated that ZUD interacted with the NF-kappaB subunit p105 and transactivator p65. Consistent with its role in inhibition of NF-kappaB-dependent transcription, ZUD sensitized cells to apoptosis induced by TNF and the TNF-related apoptosis-inducing ligand (TRAIL). Our findings suggest that ZUD is an inhibitor of NF-kappaB activation and that this protein may provide an alternative regulatory mechanism for NF-kappaB-mediated transcription.
Mesh Terms:
Apoptosis, Apoptosis Regulatory Proteins, Blotting, Northern, Carrier Proteins, Cell Line, Cloning, Molecular, Cytoplasm, Gene Deletion, Genes, Reporter, Genetic Vectors, Humans, Interleukin-1, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Microscopy, Fluorescence, Models, Genetic, Molecular Sequence Data, Mutation, NF-kappa B, Plasmids, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand, Tissue Distribution, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha
Apoptosis, Apoptosis Regulatory Proteins, Blotting, Northern, Carrier Proteins, Cell Line, Cloning, Molecular, Cytoplasm, Gene Deletion, Genes, Reporter, Genetic Vectors, Humans, Interleukin-1, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Microscopy, Fluorescence, Models, Genetic, Molecular Sequence Data, Mutation, NF-kappa B, Plasmids, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand, Tissue Distribution, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha
J. Biol. Chem.
Date: Apr. 23, 2004
PubMed ID: 14769797
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