the e3 ubiquitin ligase triad3a negatively regulates the rig-imavs signaling pathway by targeting traf3 for degradation的e3泛素连接酶triad3a负调节rig-imavs针对traf3信号通路的退化.pdfVIP

The E3 Ubiquitin Ligase Triad3A Negatively Regulates the RIG-I/MAVS Signaling Pathway by Targeting TRAF3 for Degradation 1,2 1,3 1,2 1 1 1 Peyman Nakhaei , Thibault Mesplede , Mayra Solis , Qiang Sun , Tiejun Zhao , Long Yang , Tsung- 4 5 1,3 1,2,3 Hsien Chuang , Carl F. Ware , Rongtuan Lin , John Hiscott * 1The Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada, 2 Department of Microbiology Immunology, McGill University, Montreal, Quebec, Canada, 3 Department of Medicine, McGill University, Montreal, Quebec, Canada, 4 Department of Immunology, The Scripps Research Institute, La Jolla, California, United States of America, 5 The Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California, United States of America Abstract The primary role of the innate immune response is to limit the spread of infectious pathogens, with activation of Toll-like receptor (TLR) and RIG-like receptor (RLR) pathways resulting in a pro-inflammatory response required to combat infection. Limiting the activation of these signaling pathways is likewise essential to prevent tissue injury in the host. Triad3A is an E3 ubiquitin ligase that interacts with several components of TLR signaling and modulates TLR activity. In the present study, we demonstrate that Triad3A negatively regulates the RIG-I RNA sensing pathway through Lys48-linked, ubiquitin-mediated degradation of the tumor necrosis factor receptor-associated factor 3 (TRAF3) adapter. Triad3A was induced following dsRNA exposure or virus infecti