title: Roquin--a multifunctional regulator of immune homeostasis.
abstract: Roquin-1 (Rc3h1) is an E3 ubiquitin ligase originally discovered in a mutational screen for genetic factors contributory to systemic lupus erythematosus-like symptoms in mice. A single base-pair mutation in the Rc3h1 gene resulted in the manifestation of autoantibody production and sustained immunological inflammation characterized by excessive T follicular helper cell activation and formation of germinal centers. Subsequent studies have uncovered a multifactorial process by which Roquin-1 contributes to the maintenance of immune homeostasis. Through its interactions with partner proteins, Roquin-1 targets mRNAs for decay with inducible costimulator being a primary target. In this review, we discuss newly discovered functions of Roquin-1 in the immune system and inflammation, and in disease manifestation, and discuss avenues of further research. A model is presented for the role of Roquin in health and disease.
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Schaefer
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Klein
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D009154:Mutation; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000276:immunology
chemical_list: D001323:Autoantibodies; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C000592051:RC3H1 protein, human; D016601:RNA-Binding Proteins; D018124:Receptors, Tumor Necrosis Factor; D044767:Ubiquitin-Protein Ligases