PT  - JOURNAL ARTICLE
AU  - Li, Zhi
AU  - Fan, Sijia
AU  - Wang, Jing
AU  - Chen, Xiaoyun
AU  - Liao, Qian
AU  - Liu, Xing
AU  - Ouyang, Gang
AU  - Cao, Hong
AU  - Xiao, Wuhan
TI  - Zebrafish F-box Protein fbxo3 Negatively Regulates Antiviral Response through Promoting K27-Linked Polyubiquitination of the Transcription Factors irf3 and irf7
AID  - 10.4049/jimmunol.2000305
DP  - 2020 Oct 01
TA  - The Journal of Immunology
PG  - 1897--1908
VI  - 205
IP  - 7
4099  - http://www.jimmunol.org/content/205/7/1897.short
4100  - http://www.jimmunol.org/content/205/7/1897.full
SO  - J. Immunol.2020 Oct 01; 205
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