Abstract
Tumor necrosis factor receptor-associated factor 1 (TRAF1) is unique among the members of the TRAF family, as it lacks the N-terminal RING/zinc-finger domain. Also the function of TRAF1 is not clearly established, with many papers reporting contradictory results. Here we show that TRAF1 interacts with BAFF receptor, a member of the TNF receptor family, and positively regulates activation of the alternative NF-kappaB pathway. Ectopic expression of TRAF1 causes degradation of TRAF3, stabilization of NIK, and processing of p100 to produce the mature form p52. In addition, we show that knocking-down expression of TRAF1 in the Hodgkin's disease derived cell line L1236, interfere with p100 processing and with p52 mediate gene transcription. Collectively these results support a role for TRAF1 as a positive regulator of the NF-kappaB alternative pathway.
MeSH terms
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B-Cell Activation Factor Receptor / biosynthesis*
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B-Cell Activation Factor Receptor / genetics
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B-Cell Activation Factor Receptor / immunology
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Cell Line, Tumor
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Gene Expression
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Hodgkin Disease / genetics
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Hodgkin Disease / immunology
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Hodgkin Disease / metabolism
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Humans
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NF-kappa B / genetics
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NF-kappa B / immunology
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NF-kappa B / metabolism*
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NF-kappaB-Inducing Kinase
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / immunology
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Protein Serine-Threonine Kinases / metabolism*
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Protein Stability
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TNF Receptor-Associated Factor 1 / biosynthesis*
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TNF Receptor-Associated Factor 1 / genetics
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TNF Receptor-Associated Factor 1 / immunology
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TNF Receptor-Associated Factor 3 / genetics
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TNF Receptor-Associated Factor 3 / immunology
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TNF Receptor-Associated Factor 3 / metabolism*
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Zinc Fingers / genetics
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Zinc Fingers / immunology
Substances
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B-Cell Activation Factor Receptor
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NF-kappa B
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TNF Receptor-Associated Factor 1
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TNF Receptor-Associated Factor 3
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TNFRSF13C protein, human
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TRAF3 protein, human
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Protein Serine-Threonine Kinases