| First Author | Razani B | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 4 | Pages | 422-433 |
| PubMed ID | 32205880 | Mgi Jnum | J:306576 |
| Mgi Id | MGI:6706688 | Doi | 10.1038/s41590-020-0634-4 |
| Citation | Razani B, et al. (2020) Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation. Nat Immunol 21(4):422-433 |
| abstractText | A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20(ZF7) mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20(ZF7) cells exhibited prolonged IkappaB kinase activity that drove exaggerated transcription of late-phase nuclear factor-kappaB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20's ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20's ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner. |
