DEAF1 Is a Pellino1-interacting Protein Required for Interferon Production by Sendai Virus and Double-stranded RNA

作者：Ordureau Alban; Enesa Karine; Nanda Sambit; Le Francois Brice; Peggie Mark; Prescott Alan; Albert Paul R; Cohen Philip^*

来源：Journal of Biological Chemistry, 2013, 288(34): 24569-24580.

DOI：10.1074/jbc.M113.479550

Double-stranded (ds) RNA of viral origin, a ligand for Melanoma Differentiation-associated gene 5 (MDA5) and Toll-Like Receptor 3 (TLR3), induces the TANK-Binding Kinase 1 (TBK1)-dependent phosphorylation and activation of Interferon Regulatory Factor 3 (IRF3) and the E3 ubiquitin ligase Pellino1, which are required for interferon beta (IFN beta) gene transcription. Here, we report that Pellino1 interacts with the transcription factor Deformed Epidermal Autoregulatory Factor 1 (DEAF1). The interaction is independent of the E3 ligase activity of Pellino1, but weakened by the phosphorylation of Pellino1. We show that DEAF1 binds to the IFN beta promoter and to IRF3 and IRF7, that it is required for the transcription of the IFN beta gene and IFN beta secretion in MEFs infected with Sendai virus or transfected with poly(I:C). DEAF1 is also needed for TLR3-dependent IFN beta production. Taken together, our results identify DEAF1 as a novel component of the signal transduction network by which dsRNA of viral origin stimulates IFN beta production.

• 出版日期2013-8-23