| Autor: |
Rodriguez MS; Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain., Egaña I; CIC bioGUNE, Derio, Bizkaia, Spain., Lopitz-Otsoa F; CIC bioGUNE, Derio, Bizkaia, Spain., Aillet F; Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain., Lopez-Mato MP; Cytometry and Advanced Optical Microscopy Core Facility, Inbiomed, San Sebastian, Gipuzkoa, Spain., Dorronsoro A, Lobato-Gil S; Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain., Sutherland JD; CIC bioGUNE, Derio, Bizkaia, Spain., Barrio R; CIC bioGUNE, Derio, Bizkaia, Spain., Trigueros C; Hematological Diseases, Inbiomed, San Sebastian, Gipuzkoa, Spain., Lang V; Cancer Unit, Inbiomed, San Sebastian, Gipuzkoa, Spain. |
| Abstrakt: |
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. |
