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- Title
Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex.
- Authors
Ding, Siyuan; Mooney, Nancie; Li, Bin; Kelly, Marcus R.; Feng, Ningguo; Loktev, Alexander V.; Sen, Adrish; Patton, John T.; Jackson, Peter K.; Greenberg, Harry B.
- Abstract
Rotaviruses (RVs) are the leading cause of severe gastroenteritis in young children, accounting for half a million deaths annually worldwide. RV encodes non-structural protein 1 (NSP1), a well-characterized interferon (IFN) antagonist, which facilitates virus replication by mediating the degradation of host antiviral factors including IRF3 and β-TrCP. Here, we utilized six human and animal RV NSP1s as baits and performed tandem-affinity purification coupled with high-resolution mass spectrometry to comprehensively characterize NSP1-host protein interaction network. Multiple Cullin-RING ubiquitin ligase (CRL) complexes were identified. Importantly, inhibition of cullin-3 (Cul3) or RING-box protein 1 (Rbx1), by siRNA silencing or chemical perturbation, significantly impairs strain-specific NSP1-mediated β-TrCP degradation. Mechanistically, we demonstrate that NSP1 localizes to the Golgi with the host Cul3-Rbx1 CRL complex, which targets β-TrCP and NSP1 for co-destruction at the proteasome. Our study uncovers a novel mechanism that RV employs to promote β-TrCP turnover and provides molecular insights into virus-mediated innate immunity inhibition.
- Subjects
ROTAVIRUSES; PROTEOMICS; GASTROENTERITIS; UBIQUITIN; GENE silencing; SMALL interfering RNA
- Publication
PLoS Pathogens, 2016, Vol 12, Issue 10, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1005929