Abstract
The death domain kinase RIP and the TNF receptor-associated factor 2 (TRAF2) are essential effectors in TNF signaling. To understand the mechanism by which RIP and TRAF2 regulate TNF-induced activation of the transcription factor NF-kappaB, we investigated their respective roles in TNF-R1-mediated IKK activation using both RIP-/- and TRAF2-/- fibroblasts. We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation. Moreover, we demonstrated that IKK is recruited to the TNF-R1 complex through TRAF2 upon TNF treatment and that IKK activation requires the presence of RIP in the same complex.
MeSH terms
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Antigens, CD / analysis
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Antigens, CD / chemistry
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Antigens, CD / physiology*
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Apoptosis / physiology*
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Cells, Cultured
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Enzyme Activation
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Fibroblasts / cytology
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Humans
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I-kappa B Kinase
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Macromolecular Substances
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NF-kappa B / physiology*
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / physiology*
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Proteins / physiology*
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Receptor-Interacting Protein Serine-Threonine Kinases
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Receptors, Tumor Necrosis Factor / analysis
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Receptors, Tumor Necrosis Factor / chemistry
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Receptors, Tumor Necrosis Factor / physiology*
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins / physiology
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Signal Transduction / physiology*
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TNF Receptor-Associated Factor 2
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Transcription, Genetic*
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Transfection
Substances
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Antigens, CD
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Macromolecular Substances
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NF-kappa B
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Proteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins
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TNF Receptor-Associated Factor 2
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Protein Serine-Threonine Kinases
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RIPK1 protein, human
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Receptor-Interacting Protein Serine-Threonine Kinases
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human