title: TRAF7 protein promotes Lys-29-linked polyubiquitination of IkappaB kinase (IKKgamma)/NF-kappaB essential modulator (NEMO) and p65/RelA protein and represses NF-kappaB activation.
abstract: Tumor necrosis factor receptor-associated factor (TRAF) proteins are cytoplasmic regulatory molecules that function as signal transducers for receptors involved in both innate and adaptive humoral immune responses. In this study, we show that TRAF7, the unique noncanonical member of the TRAF family, physically associates with IκB kinase/NF-κB essential modulator (NEMO) and with the RelA/p65 (p65) member of the NF-κB transcription factor family. TRAF7 promotes Lys-29-linked polyubiquitination of NEMO and p65 that results in lysosomal degradation of both proteins and altered activation. TRAF7 also influences p65 nuclear distribution. Microarray expression data are consistent with an inhibitory role for TRAF7 on NF-κB and a positive control of AP-1 transcription factor. Finally, functional data indicate that TRAF7 promotes cell death. Thus, this study identifies TRAF7 as a NEMO- and p65-interacting molecule and brings important information on the ubiquitination events that control NF-κB transcriptional activity.
authors.affiliation: Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Zotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Uva
authors.forename: Angela
authors.initials: A
authors.lastname: Ferravante
authors.forename: Mariangela
authors.initials: M
authors.lastname: Vessichelli
authors.forename: Ivan
authors.initials: I
authors.lastname: Scudiero
authors.forename: Michele
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Vito
authors.forename: Romania
authors.initials: R
authors.lastname: Stilo
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D056704:Adaptive Immunity / Q000502:physiology; D016923:Cell Death; D002467:Cell Nucleus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology; D008247:Lysosomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: C491731:IKBKG protein, human; C498143:RELA protein, human; C486460:TRAF7 protein, human; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D051550:I-kappa B Kinase