Japanese Journal of Clinical Immunology
Online ISSN : 1349-7413
Print ISSN : 0911-4300
ISSN-L : 0911-4300
Review Articles
Autoimmune diseases and ubiquitin system
Shigeru OSHIMA
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2017 Volume 40 Issue 6 Pages 442-449


  Cytokines play important roles in the pathogenesis of autoimmune diseases. Anti-TNFα antibody therapy for rheumatoid arthritis, Crohn's disease, and psoriasis has made enough progress to change its treatment goal. This review focuses on the recent advances that have been made in understanding TNFR signaling through ubiquitin system. Genome-wide association studies (GWAS) identified numerous susceptibility loci associated with autoimmune diseases. Ubiquitin related genes TNFAIP3 and TNIP1 have been linked to multiple autoimmune diseases. Here, we review the importance of TNFAIP3 and TNIP1-mediated regulation of ubiquitin-dependent signaling. To monitor the dynamics of ubiquitin chain formation in vivo, we have developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay. The PolyUb-FC assay has the advantage that monoubiquitination is non-fluorescent and chain-specific poly-ubiquitination can be directly visualized in living cells without using antibodies. The PolyUb-FC will be a useful tool for analyzing the dynamics of polyubiquitin chain generation.

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© 2017 The Japan Society for Clinical Immunology
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