Viral infection is a serious threat to both normal population and clinical patients. plays central roles in host defense against viral infection. How duanyu18131 protein maintains stable in different conditions remains largely unknown. Here, we identified BRCC36 as a potent regulator of duanyu18131 protein stability. Mechanistically, BRCC36 maintains duanyu18131 levels by utilizing USP13 to form a balanced complex for antagonizing Smurf1-mediated degradation. Importantly, cellular BRCC36 deficiency results in rapid downregulation of duanyu18131 during viral infection, whereas a supplement of BRCC36 maintains duanyu18131 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 duanyu18131 stability. This study uncovers a critical role of BRCC36 in duanyu18131 protein stability and could provide potential strategies for enhancing clinical antiviral therapy.
KEYWORDS: BRCC36, HSC transplantation, IFN, STAT1, antiviral immunity