BRCC36 functions noncatalytically to promote antiviral response by maintaining STAT1 protein stability. Issue 2 (23rd August 2020)

• Record Type: Journal Article
• Authors: Cheng, Qiao; Feng, Qian; Xu, Yang; Zuo, Yibo; Liu, Jin; Yuan, Yukang; Miao, Ying; Liu, Yin; Lei, Lei; Guo, Tingting; Zhang, Liting; Wu, Depei; Zheng, Hui
• Is Part Of: European journal of immunology. Volume 51:Issue 2(2021)
• Page Start: 296
• Page End: 310
• Publication Date: 2020-08-23
• Subjects: antiviral immunity -- BRCC36 -- HSC transplantation -- IFN -- STAT1; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048537
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Viral infection is a serious threat to both normal population and clinical patients. STAT1 plays central roles in host defense against viral infection. How STAT1 protein maintains stable in different conditions remains largely unknown. Here, we identified BRCC36 as a potent regulator of STAT1 protein stability. Mechanistically, BRCC36 maintains STAT1 levels by utilizing USP13 to form a balanced complex for antagonizing Smurf1‐mediated degradation. Importantly, cellular BRCC36 deficiency results in rapid downregulation of STAT1 during viral infection, whereas a supplement of BRCC36 maintains STAT1 protein levels and host antiviral immunity in vivo. Moreover, we revealed that BRCC36 expression was downregulated in allogeneic HSC transplantation (allo‐HSCT) mice that showed increased susceptibility to viral infection. Supplementing BRCC36 enhanced antiviral response of allo‐HSCT mice by maintaining STAT1 stability. This study uncovers a critical role of BRCC36 in STAT1 protein stability and could provide potential strategies for enhancing clinical antiviral therapy. Abstract : BRCC36 maintains cellular STAT1 protein stability by forming a balanced complex with Smurf1 and USP13, revealing a delicate regulatory mechanism of STAT1 protein levels.