title: A protein-kinase, IFN-inducible double-stranded RNA dependent inhibitor and repressor of p58 (PRKRIR) enhances type I IFN-mediated antiviral response through the stability control of RIG-I protein.
abstract: The cellular RIG-I-like receptor (RLR) senses pathogenic RNA molecular patterns and transmits signals for type I interferon (IFN) production. It acts as a center for antiviral responses, and large numbers of RIG-I (retinoic acid inducible gene-I) interacting proteins are identified as signaling regulators. In the present study, we report PRKRIR, a negative regulator of PKR inhibitor, as a novel RIG-I interacting protein. In HEK293FT cells, PRKRIR synergistically enhances type I IFN production mediated by a signal activated- or constitutively active form of RIG-I. The C-terminal domain of the PRKRIR was required for physical interaction and the signal augmentation. The PRKRIR blocks poly-ubiquitination and protein degradation of RIG-I, thereby increasing cellular levels of RIG-I proteins. Furthermore, overexpression of PRKRIR, along with a signal activated- or constitutively active form of RIG-I, efficiently inhibits virus replication in the infected host. In conclusion, PRKRIR provides a novel positive regulator controlling the RIG-I-IFN production system through protein stability control.
authors.affiliation: Department of Life Sciences, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Hesung
authors.initials: H
authors.lastname: Now
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Yoo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000276:immunology*; D055550:Protein Stability; D012328:RNA Viruses / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000378:metabolism*; D011971:Receptors, Immunologic; D054875:Ubiquitination; D014779:Virus Replication / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; C110409:THAP12 protein, human; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases