A20, or tumor necrosis factor α-induced protein 3 (TNFAIP3), is a zinc finger ubiquitin editing anti-inflammatory enzyme that modulates immune responses and apoptosis. Mutations in A20 and A20 haploinsufficiency have been linked to several autoimmune and autoinflammatory diseases1-4, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriatic arthritis5-7. Studies utilizing animal models have confirmed roles for A20 in the pathogenesis of autoinflammatory and RA-like diseases and helped to identify the mechanisms involved8, 9. The first identified mechanism by which A20 exerts its anti-inflammatory effect was through the inhibition of NF-κB activation10. Additional mechanisms by which the enzymatic function of A20 offers protection for autoinflammatory conditions have been reported, including inhibition of necroptosis by deubiquitinating receptor-interacting protein kinase 3 (RIPK3)11 (See Figure 1).
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory arthritis and a variety of systemic manifestations. The addition of immunosuppressant biologics to classic disease-modifying antirheumatic drugs (DMARDs) has improved the management of RA12. However, there is no cure, and the underlying mechanisms of disease pathogenesis remain to be fully elucidated. In recent years, two ubiquitin-binding domains, zinc finger 4 (ZnF4) and ZnF7, in the A20 protein have been shown to be essential for inhibiting inflammation-dependent arthritis9, 13. This newsletter will review evidence that unveiled the importance of A20 ubiquitin-binding in RA and related arthritic disorders.
Also included in this newsletter:
- Actin and Microtubule Tools
- Related Publications