TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that mediates activation of the transcription factor NF-kappaB.
We describe the cloning and characterization of tumor necrosis factor receptor (TNF-R)-associated ubiquitous scaffolding and signaling protein (TRUSS), a novel TNF-R1-interacting protein of 90.7 kDa. TRUSS mRNA was ubiquitously expressed in mouse tissues but was enriched in heart, liver, and testis. Co-immunoprecipitation experiments showed that TRUSS was constitutively associated with ... unligated TNF-R1 and that the complex was relatively insensitive to stimulation with TNF-alpha. Deletion mutagenesis of TNF-R1 indicated that TRUSS interacts with both the membrane-proximal region and the death domain of TNF-R1. In addition, the N-terminal region of TRUSS (residues 1 to 440) contains sequences that permit association with the cytoplasmic domain of TNF-R1. Transient overexpression of TRUSS activated NF-kappaB and increased NF-kappaB activation in response to ligation of TNF-R1. In contrast, a COOH-terminal-deletion mutant of TRUSS (TRUSS(1-723)) was found to inhibit NF-kappaB activation by TNF-alpha. Co-precipitation and co-immunoprecipitation assays revealed that TRUSS can interact with TRADD, TRAF2, and components of the IKK complex. These findings suggest that TRUSS may serve as a scaffolding protein that interacts with TNF-R1 signaling proteins and may link TNF-R1 to the activation of IKK.
Mesh Terms:
Amino Acid Sequence, Animals, Antigens, CD, Binding Sites, COS Cells, Cell Line, Cloning, Molecular, Humans, Male, Mice, Molecular Sequence Data, NF-kappa B, NIH 3T3 Cells, Proteins, RNA, Messenger, Receptor-Interacting Protein Serine-Threonine Kinases, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Recombinant Proteins, Sequence Deletion, TNF Receptor-Associated Death Domain Protein, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, Trans-Activators, Transcriptional Activation, Transfection, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Tumor Necrosis Factor-alpha
Amino Acid Sequence, Animals, Antigens, CD, Binding Sites, COS Cells, Cell Line, Cloning, Molecular, Humans, Male, Mice, Molecular Sequence Data, NF-kappa B, NIH 3T3 Cells, Proteins, RNA, Messenger, Receptor-Interacting Protein Serine-Threonine Kinases, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Recombinant Proteins, Sequence Deletion, TNF Receptor-Associated Death Domain Protein, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, Trans-Activators, Transcriptional Activation, Transfection, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Tumor Necrosis Factor-alpha
Mol. Cell. Biol.
Date: Nov. 01, 2003
PubMed ID: 14585990
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