2021年1月，吴德沛教授、郑慧教授课题组在《European Journal of Immunology》杂志发表最新研究成果“BRCC36 functions noncatalytically topromote antiviral response by maintaining STAT1 protein stability”。该研究证明去泛素化酶BRCC3通过维持STAT1蛋白稳定性从而促进抗病毒免疫应答。

病毒感染严重威胁正常人群和临床患者的健康。STAT1在宿主抵抗病毒感染的防御中起着核心作用，但STAT1蛋白在不同条件下如何保持稳定仍然不清楚。本研究中，我们发现BRCC36是STAT1蛋白稳定性的有效调节剂。机制方面，我们证实BRCC36通过利用USP13形成一个平衡的复合物来拮抗Smurf1介导的降解来维持STAT1的水平。重要的是，在病毒感染情况下，细胞内BRCC36缺乏会导致STAT1蛋白快速降解。动物实验表明，补充BRCC3即可维持STAT1蛋白水平并增强小鼠抗病毒免疫功能。此外，我们发现异基因造血干细胞移植（allo-HSCT）小鼠中BRCC36表达也显著下调，并且allo-HSCT小鼠对病毒感染的敏感性增加。进一步，我们发现补充BRCC36可以通过维持STAT1蛋白稳定性从而增强allo-HSCT小鼠的抗病毒免疫反应。这项研究揭示了BRCC36在STAT1蛋白稳定性中的关键作用，并可能为临床抗病毒免疫治疗提供潜在的策略。

原文摘要：Viral infection is a seriousthreat to both normal population and clinical patients. STAT1 plays centralroles in host defense against viral infection. How STAT1 protein maintainsstable in different conditions remains largely unknown. Here, we identifiedBRCC36 as a potent regulator of STAT1 protein stability. Mechanistically,BRCC36 maintains STAT1 levels by utilizing USP13 to form a balanced complex forantagonizing Smurf1-mediated degradation. Importantly, cellular BRCC36deficiency results in rapid downregulation of STAT1 during viral infection,whereas a supplement of BRCC36 maintains STAT1 protein levels and hostantiviral immunity in vivo. Moreover, we revealed that BRCC36 expression wasdownregulated in allogeneic HSC transplantation (allo-HSCT) mice that showedincreased susceptibility to viral infection. Supplementing BRCC36 enhancedantiviral response of allo-HSCT mice by maintaining STAT1 stability. This studyuncovers a critical role of BRCC36 in STAT1 protein stability and could providepotential strategies for enhancing clinical antiviral therapy.