PUBLICATION

Zebrafish F-box Protein fbxo3 Negatively Regulates Antiviral Response through Promoting K27-Linked Polyubiquitination of the Transcription Factors irf3 and irf7

Authors
Li, Z., Fan, S., Wang, J., Chen, X., Liao, Q., Liu, X., Ouyang, G., Cao, H., Xiao, W.
ID
ZDB-PUB-200830-8
Date
2020
Source
Journal of immunology (Baltimore, Md. : 1950)   205(7): 1897-1908 (Journal)
Registered Authors
Cao, Hong, Li, Zhi, Ouyang, Gang, Wang, Jing, Xiao, Wuhan
Keywords
none
MeSH Terms
  • Animals
  • Cells, Cultured
  • F-Box Proteins/genetics
  • F-Box Proteins/metabolism*
  • Fish Proteins/genetics
  • Fish Proteins/metabolism*
  • Immunity, Innate
  • Interferon Regulatory Factor-3/metabolism*
  • Interferon Regulatory Factors/metabolism*
  • Lysine/genetics
  • Proteolysis
  • Rhabdoviridae/physiology*
  • Rhabdoviridae Infections/immunology*
  • Signal Transduction
  • Ubiquitination
  • Zebrafish/immunology*
  • Zebrafish/virology
  • Zebrafish Proteins/metabolism*
PubMed
32859728 Full text @ J. Immunol.
Abstract
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.
Errata / Notes
This article is corrected by both ZDB-PUB-201208-37, and ZDB-PUB-210716-2.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping