title: TNF receptor-associated factor 1 is a positive regulator of the NF-kappaB alternative pathway.
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.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II University of Naples, Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lavorgna
authors.forename: Rosaria
authors.initials: R
authors.lastname: De Filippi
authors.forename: Silvestro
authors.initials: S
authors.lastname: Formisano
authors.forename: Antonio
authors.initials: A
authors.lastname: Leonardi
mesh_terms: D053265:B-Cell Activation Factor Receptor / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D015870:Gene Expression; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055550:Protein Stability; D047990:TNF Receptor-Associated Factor 1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D053265:B-Cell Activation Factor Receptor; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D047990:TNF Receptor-Associated Factor 1; D048008:TNF Receptor-Associated Factor 3; D000097782:NF-kappaB-Inducing Kinase; C435926:TNFRSF13C protein, human; C090656:TRAF3 protein, human