The RING ubiquitin E3 RNF114 interacts with A20 and modulates NF-κB activity and T-cell activation

• Published in: Cell death & disease 2014-08, Vol.5 (8), p.e1399-e1399
• Main Authors: Rodriguez, M S, Egaña, I, Lopitz-Otsoa, F, Aillet, F, Lopez-Mato, M P, Dorronsoro, A, Lobato-Gil, S, Sutherland, J D, Barrio, R, Trigueros, C, Lang, V
• Format: Article
• Language: English
• Subjects: 631/250/1619/554; 631/250/249/2510; 631/80/82/23; 631/80/86; Antibodies; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology; Cell Culture; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; HEK293 Cells; Humans; I-kappa B Proteins - metabolism; Immunology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Jurkat Cells; Life Sciences; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Original; original-article; Protein Binding; RNA Interference; RNA, Small Interfering - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transcription, Genetic; Tumor Necrosis Factor alpha-Induced Protein 3; Tumor Necrosis Factor-alpha - pharmacology; Ubiquitination
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2014.366

Accurate regulation of nuclear factor- κ B (NF- κ B) activity is crucial to prevent a variety of disorders including immune and inflammatory diseases. Active NF- κ B promotes I κ B α and A20 expression, important negative regulatory molecules that control the NF- κ B 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- κ B-dependent transcription, not only by stabilizing the A20 protein but also I κ B α . 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- κ B activity that contributes to the control of signaling pathways modulating T cell-mediated immune response.