The Sjögren’s Syndrome-Associated Autoantigen Ro52 Is an E3 Ligase That Regulates Proliferation and Cell Death
Open Access
- 15 May 2006
- journal article
- Published by The American Association of Immunologists
- Vol. 176 (10), 6277-6285
- https://doi.org/10.4049/jimmunol.176.10.6277
Abstract
Patients affected by Sjögren’s syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52. Although the serologic presence of Ro52 autoantibodies is used clinically for diagnostic purposes, the function of the protein or why it is targeted as an autoantigen in several rheumatic conditions has not been elucidated. In this study, we show that the expression of Ro52 is significantly increased in PBMC of patients with Sjögren’s syndrome and SLE, and demonstrate that Ro52 is a RING-dependent E3 ligase involved in ubiquitination. Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway. The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability. These findings suggest that the increased expression of the Ro52 autoantigen in patients may be directly involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sjögren’s syndrome and SLE, and may thus contribute to the autoantigenic load and induction of autoimmune B and T cell responses observed in rheumatic patients.Keywords
This publication has 43 references indexed in Scilit:
- Topors Functions as an E3 Ubiquitin Ligase with Specific E2 Enzymes and Ubiquitinates p53Journal of Biological Chemistry, 2004
- RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase propertiesCarcinogenesis: Integrative Cancer Research, 2003
- Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosusArthritis & Rheumatism, 2003
- Structural basis of ubiquitylationCurrent Opinion in Structural Biology, 2002
- Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndromeArthritis & Rheumatism, 2002
- Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus GroupAnnals Of The Rheumatic Diseases, 2002
- Abnormal B Cell Differentiation in Primary Sjögren's Syndrome Results in a Depressed Percentage of Circulating Memory B Cells and Elevated Levels of Soluble CD27 That Correlate with Serum IgG ConcentrationClinical Immunology, 2002
- Receptor and Non-Receptor Mediated Actions of MelatoninNeurosignals, 2000
- Cytoplasmic Accumulation of the 52kDa Ro/SS-A Nuclear Autoantigen in Transfected Cell LinesJournal of Autoimmunity, 1995
- Antibodies to Murine CD40 Stimulate Normal B Lymphocytes but Inhibit Proliferation of B Lymphoma CellsCellular Immunology, 1993