BRCC36 functions noncatalytically to promote antiviral response by maintaining STAT1 protein stability.

European Journal of Immunology
Qiao ChengHui Zheng

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.

References

Sep 5, 2002·Nature Reviews. Molecular Cell Biology·David E Levy, J E Darnell
Jan 23, 2004·PLoS Biology·Xavier I AmbroggioRaymond J Deshaies
May 26, 2007·Science·Bijan SobhianRoger A Greenberg
Mar 6, 2009·Genes & Development·Genze ShaoRoger A Greenberg
May 14, 2009·The Journal of Clinical Investigation·Ariane ChapgierJean-Laurent Casanova
Dec 25, 2009·The Journal of Biological Chemistry·Eric M CooperRobert E Cohen
Apr 24, 2012·Immunity·George R Stark, James E Darnell
Dec 19, 2012·Molecular Cell·Bénédicte F PyJunying Yuan
Aug 14, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hom-Ming YehYi-Ling Lin
Oct 1, 2013·Cell Reports·Hui ZhengRoger A Greenberg
Dec 30, 2015·The Journal of Experimental Medicine·Steven M HeatonVishva M Dixit
Jun 12, 2016·The Journal of Biological Chemistry·Hoi-Man NgMichael S Y Huen
Jul 27, 2017·European Journal of Immunology·Yilong ZhouBaoxue Ge
Apr 12, 2019·Transplant Infectious Disease : an Official Journal of the Transplantation Society·Hayley E CunninghamAnne M Lachiewicz
May 28, 2019·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Bradley FigginsJason Yeh
May 31, 2019·Nature·Miriam WaldenElton Zeqiraj
Jun 30, 2019·Molecular Cell·Julius RablNicolas H Thomä

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