Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB.

Abstract

A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB.

• Authors: Kristin Burles, Nicholas van Buuren, Michele Barry
• Journal: Virology (Virology) Vol. 468-470 Pg. 351-362 (Nov 2014) ISSN: 1096-0341 [Electronic] United States
• PMID: 25240225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Ankyrins
• F-Box Proteins
• NF-kappa B
• Viral Proteins
• SKP Cullin F-Box Protein Ligases
• I-kappa B Kinase

Topics

• Active Transport, Cell Nucleus (physiology)
• Ankyrins (genetics, metabolism)
• Cell Line
• Ectromelia virus (genetics, metabolism)
• F-Box Proteins (genetics, metabolism)
• Gene Expression Regulation, Viral (physiology)
• Humans
• I-kappa B Kinase (genetics, metabolism)
• Multigene Family
• NF-kappa B (metabolism)
• Plasmids
• SKP Cullin F-Box Protein Ligases (genetics, metabolism)
• Viral Proteins (genetics, metabolism)