title: The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation.
abstract: Accurate regulation of nuclear factor-κB (NF-κB) activity is crucial to prevent a variety of disorders including immune and inflammatory diseases. Active NF-κB promotes IκBα and A20 expression, important negative regulatory molecules that control the NF-κB response. In this study, using two-hybrid screening we identify the RING-type zinc-finger protein 114 (RNF114) as an A20-interacting factor. RNF114 interacts with A20 in T cells and modulates A20 ubiquitylation. RNF114 acts as negative regulator of NF-κB-dependent transcription, not only by stabilizing the A20 protein but also IκBα. Importantly, we demonstrate that in T cells, the effect of RNF114 is linked to the modulation of T-cell activation and apoptosis but is independent of cell cycle regulation. Altogether, our data indicate that RNF114 is a new partner of A2O involved in the regulation of NF-κB activity that contributes to the control of signaling pathways modulating T cell-mediated immune response.
authors.affiliation: Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain.
authors.forename: M S
authors.initials: MS
authors.lastname: Rodriguez
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Egaña
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Lopitz-Otsoa
authors.affiliation: Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Aillet
authors.affiliation: Cytometry and Advanced Optical Microscopy Core Facility, Inbiomed, San Sebastian, Gipuzkoa, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Lopez-Mato
authors.forename: A
authors.initials: A
authors.lastname: Dorronsoro
authors.affiliation: Hematological Diseases, Inbiomed, San Sebastian, Gipuzkoa, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Dorronroso
authors.affiliation: Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Lobato-Gil
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: J D
authors.initials: JD
authors.lastname: Sutherland
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Barrio
authors.affiliation: Hematological Diseases, Inbiomed, San Sebastian, Gipuzkoa, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Trigueros
authors.affiliation: Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Lang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C477146:RNF114 protein, human; D044767:Ubiquitin-Protein Ligases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3