A Deubiquitinase That Regulates Type I Interferon Production

• DOI: 10.1126/science.1145918
• Publication Date: 2007-11-09T01:45:29Z
• Authors: Nobuhiko Kayagaki; Qui Phung; Salina Chan; Ruchir Chaudhari; Casey Quan; Karen M. O'Rourke; Michael Eby; Eric Pietras; Genhong Cheng; J. Fernando Bazan; Zemin Zhang; David Arnott; Vishva M. Dixit
• Keywords: Deubiquitinating enzyme; Ectopic expression; ISG15

Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in small interfering RNA–based screen as regulator IFN-I production. Reduction DUBA augmented PRR-induced response, whereas ectopic expression had converse effect. bound necrosis factor receptor–associated 3 (TRAF3), adaptor protein essential for response. TRAF3 E3 ubiquitin ligase that preferentially assembled lysine-63–linked polyubiquitin chains. selectively cleaved chains on TRAF3, resulting its dissociation from downstream signaling complex containing TANK-binding kinase 1. discrete interaction motif within required efficient deubiquitination and optimal suppression IFN-I. Our data identify negative responses.