RT Journal Article
SR Electronic
T1 Zebrafish F-box Protein fbxo3 Negatively Regulates Antiviral Response through Promoting K27-Linked Polyubiquitination of the Transcription Factors irf3 and irf7
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 1897
OP 1908
DO 10.4049/jimmunol.2000305
VO 205
IS 7
A1 Li, Zhi
A1 Fan, Sijia
A1 Wang, Jing
A1 Chen, Xiaoyun
A1 Liao, Qian
A1 Liu, Xing
A1 Ouyang, Gang
A1 Cao, Hong
A1 Xiao, Wuhan
YR 2020
UL http://www.jimmunol.org/content/205/7/1897.abstract
AB Zebrafish fbxo3 negatively regulates antiviral responses.Zebrafish fbxo3 inhibits expression of antiviral response genes upon SVCV infection.Zebrafish fbxo3 promotes degradation of irf3 and irf7 by catalyzing ubiquitination.FBXO3, belongs to the F-box family of proteins, which has been reported to involve in host autoimmune and inflammatory responses by promoting its substrates for ubiquitylation. However, thus far, its physiological function in antiviral immunity remains elusive. In this study, we report that overexpression of zebrafish fbxo3 suppresses cellular antiviral responses. Moreover, disruption of fbxo3 in zebrafish increases the survival rate upon spring viremia of carp virus exposure. Further assays indicate that fbxo3 interacts with irf3/irf7 and specifically catalyzes K27-linked ubiquitination of irf3 and irf7, resulting in proteasomal degradation of irf3 and irf7. However, the F-box domain of fbxo3 is not required for fbxo3 to interact with irf3/irf7 and to inhibit transactivity of irf3 and irf7. This study provides novel insights into fbxo3 function and the underlying mechanisms. In addition, it sheds new light on the regulation of IFN-I signaling by F-box proteins.This article is featured in Top Reads, p.1719