Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis
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Apoptosis Regulatory Proteins
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Blotting, Northern
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / physiology*
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Cell Line
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Cloning, Molecular
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Cytoplasm / metabolism
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Gene Deletion
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Genes, Reporter
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Genetic Vectors
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Humans
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Interleukin-1 / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins / metabolism
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Microscopy, Fluorescence
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Models, Genetic
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Molecular Sequence Data
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Mutation
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NF-kappa B / antagonists & inhibitors*
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Plasmids / metabolism
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Precipitin Tests
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Protein Binding
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Protein Structure, Tertiary
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Signal Transduction
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TNF-Related Apoptosis-Inducing Ligand
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Tissue Distribution
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Transcription, Genetic
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Transcriptional Activation
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Transfection
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Apoptosis Regulatory Proteins
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Carrier Proteins
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Interleukin-1
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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NF-kappa B
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tnfsf10 protein, mouse
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Tumor Necrosis Factor-alpha
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UNC5CL protein, human
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Unc5cl protein, mouse
Associated data
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GENBANK/AY510108
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GENBANK/AY510109