The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation
Autor: | Lobato-Gil S, Lopez-Mato Mp, Egaña I, Manuel S. Rodriguez, Akaitz Dorronsoro, César Trigueros, James D. Sutherland, Fabienne Aillet, Fernando Lopitz-Otsoa, Rosa Barrio, Lang |
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Předmět: |
Cancer Research
Transcription Genetic T-Lymphocytes Ubiquitin-Protein Ligases T cell Immunology Apoptosis Biology Jurkat cells Jurkat Cells Cellular and Molecular Neuroscience chemistry.chemical_compound NF-KappaB Inhibitor alpha immune system diseases hemic and lymphatic diseases medicine Humans RNA Small Interfering Nuclear protein Tumor Necrosis Factor alpha-Induced Protein 3 Tumor Necrosis Factor-alpha Intracellular Signaling Peptides and Proteins NF-kappa B Ubiquitination Nuclear Proteins NF-κB Cell Biology NFKB1 Molecular biology Cell biology DNA-Binding Proteins IκBα HEK293 Cells medicine.anatomical_structure chemistry Original Article I-kappa B Proteins RNA Interference Signal transduction Corrigendum Carrier Proteins Protein Binding |
Zdroj: | Europe PubMed Central Cell Death & Disease |
Popis: | 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. |
Databáze: | OpenAIRE |
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