Vereecke Lars, Beyaert Rudi, van Loo Geert
Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent B-9052, Belgium.
Trends Immunol. 2009 Aug;30(8):383-91. doi: 10.1016/j.it.2009.05.007. Epub 2009 Jul 28.
Nuclear factor (NF)-kappaB has an important role in immunity and inappropriate NF-kappaB activity has been linked with many autoimmune and inflammatory diseases. Multiple mechanisms normally ensure the proper termination of NF-kappaB activation. In this context, the intracellular ubiquitin-editing protein A20 (also known as Tumor Necrosis Factor Alpha-Induced Protein 3 or TNFAIP3) is a key player in the negative feedback regulation of NF-kappaB signaling in response to multiple stimuli. Moreover, A20 also regulates tumor necrosis factor (TNF)-induced apoptosis. Recent genetic studies demonstrate a clear association between several mutations in the human A20 locus and immunopathologies such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and type 1 diabetes. These findings further illustrate the importance of A20 in the resolution of inflammation and the prevention of human disease.
核因子（NF）-κB在免疫中发挥重要作用，而NF-κB的异常激活与许多自身免疫性疾病和炎症性疾病相关。多种机制通常可确保NF-κB激活的适当终止。在此背景下，细胞内泛素编辑蛋白A20（也称为肿瘤坏死因子α诱导蛋白3或TNFAIP3）是响应多种刺激时NF-κB信号负反馈调节的关键因子。此外，A20还调节肿瘤坏死因子（TNF）诱导的细胞凋亡。最近的遗传学研究表明，人类A20基因座的多个突变与诸如克罗恩病、类风湿性关节炎、系统性红斑狼疮、牛皮癣和1型糖尿病等免疫病理学之间存在明确关联。这些发现进一步说明了A20在炎症消退和预防人类疾病中的重要性。
