Identification of a ZU5 and death domain-containing inhibitor of NF-kappaB

J Biol Chem. 2004 Apr 23;279(17):17819-25. doi: 10.1074/jbc.M310737200. Epub 2004 Feb 9.


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

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

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Blotting, Northern
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology*
  • Cell Line
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • Gene Deletion
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • Interleukin-1 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / metabolism
  • Microscopy, Fluorescence
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • NF-kappa B / antagonists & inhibitors*
  • Plasmids / metabolism
  • 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 / metabolism


  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Interleukin-1
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • NF-kappa B
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • UNC5CL protein, human
  • Unc5cl protein, mouse

Associated data

  • GENBANK/AY510108
  • GENBANK/AY510109