| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Rheumatology Unit, Department of Medicine and
Department of Dermatology, Karolinska Institutet at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden; and
Center for Neurologic Diseases, Brigham and Woman’s Hospital, Harvard Medical School, Boston, MA 02115
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.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  R. Yoshimi, T.-H. Chang, H. Wang, T. Atsumi, H. C. Morse III, and K. Ozato Gene Disruption Study Reveals a Nonredundant Role for TRIM21/Ro52 in NF-{kappa}B-Dependent Cytokine Expression in Fibroblasts J. Immunol., June 15, 2009; 182(12): 7527 - 7538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yang, H.-X. Shi, X.-Y. Liu, Y.-F. Shan, B. Wei, S. Chen, and C. Wang TRIM21 Is Essential to Sustain IFN Regulatory Factor 3 Activation during Antiviral Response J. Immunol., March 15, 2009; 182(6): 3782 - 3792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Kim and K. Ozato The Sequestosome 1/p62 Attenuates Cytokine Gene Expression in Activated Macrophages by Inhibiting IFN Regulatory Factor 8 and TNF Receptor-Associated Factor 6/NF-{kappa}B Activity J. Immunol., February 15, 2009; 182(4): 2131 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Higgs, J. N. Gabhann, N. B. Larbi, E. P. Breen, K. A. Fitzgerald, and C. A. Jefferies The E3 Ubiquitin Ligase Ro52 Negatively Regulates IFN-{beta} Production Post-Pathogen Recognition by Polyubiquitin-Mediated Degradation of IRF3 J. Immunol., August 1, 2008; 181(3): 1780 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Miyajima, S. Maruyama, M. Bohgaki, S. Kano, M. Shigemura, N. Shinohara, K. Nonomura, and S. Hatakeyama TRIM68 Regulates Ligand-Dependent Transcription of Androgen Receptor in Prostate Cancer Cells Cancer Res., May 1, 2008; 68(9): 3486 - 3494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Barkauskaite, M. Ek, K. Popovic, H.E. Harris, M. Wahren-Herlenius, and F. Nyberg Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus Lupus, October 1, 2007; 16(10): 794 - 802. [Abstract] [PDF]
|
|
|
|
|
|
H. J. Kong, D. E. Anderson, C. H. Lee, M. K. Jang, T. Tamura, P. Tailor, H. K. Cho, J. Cheong, H. Xiong, H. C. Morse III, et al. Cutting Edge: Autoantigen Ro52 Is an Interferon Inducible E3 Ligase That Ubiquitinates IRF-8 and Enhances Cytokine Expression in Macrophages J. Immunol., July 1, 2007; 179(1): 26 - 30. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
