Comparative Proteomics Reveals Strain-Specific beta-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex

文献类型： 外文期刊

第一作者： Ding, Siyuan

作者： Ding, Siyuan;Mooney, Nancie;Kelly, Marcus R.;Feng, Ningguo;Loktev, Alexander V.;Sen, Adrish;Jackson, Peter K.;Greenberg, Harry B.;Ding, Siyuan;Li, Bin;Feng, Ningguo;Sen, Adrish;Greenberg, Harry B.;Ding, Siyuan;Li, Bin;Feng, Ningguo;Sen, Adrish;Greenberg, Harry B.;Mooney, Nancie;Kelly, Marcus R.;Loktev, Alexander V.;Jackson, Peter K.;Li, Bin;Patton, John T.

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：6.823； 五年影响因子：7.455 ）

ISSN： 1553-7366

年卷期： 2016 年 12 卷 10 期

页码：

收录情况： SCI

摘要： 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 beta-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 beta-TrCP degradation. Mechanistically, we demonstrate that NSP1 localizes to the Golgi with the host Cul3-Rbx1 CRL complex, which targets beta-TrCP and NSP1 for co-destruction at the proteasome. Our study uncovers a novel mechanism that RV employs to promote beta-TrCP turnover and provides molecular insights into virus-mediated innate immunity inhibition.

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