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Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex
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نویسنده
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ding s. ,mooney n. ,li b. ,kelly m.r. ,feng n. ,loktev a.v. ,sen a. ,patton j.t. ,jackson p.k. ,greenberg h.b.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 10
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چکیده
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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. © 2016 public library of science. all rights reserved.
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آدرس
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department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,department of medicine,division of gastroenterology and hepatology,stanford university school of medicine,stanford,ca,united states,palo alto veterans institute of research,va palo alto health care system,palo alto,ca, United States, department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,baxter laboratory for stem cell biology,stanford university school of medicine,stanford,ca, United States, department of medicine,division of gastroenterology and hepatology,stanford university school of medicine,stanford,ca,united states,palo alto veterans institute of research,va palo alto health care system,palo alto,ca,united states,institute of veterinary medicine,jiangsu academy of agricultural sciences,nanjing, China, department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,baxter laboratory for stem cell biology,stanford university school of medicine,stanford,ca, United States, department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,department of medicine,division of gastroenterology and hepatology,stanford university school of medicine,stanford,ca,united states,palo alto veterans institute of research,va palo alto health care system,palo alto,ca, United States, department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,baxter laboratory for stem cell biology,stanford university school of medicine,stanford,ca, United States, department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,department of medicine,division of gastroenterology and hepatology,stanford university school of medicine,stanford,ca,united states,palo alto veterans institute of research,va palo alto health care system,palo alto,ca, United States, department of veterinary medicine,university of maryland,college park,md, United States, department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,baxter laboratory for stem cell biology,stanford university school of medicine,stanford,ca, United States, department of microbiology and immunology,stanford university school of medicine,stanford,ca,united states,department of medicine,division of gastroenterology and hepatology,stanford university school of medicine,stanford,ca,united states,palo alto veterans institute of research,va palo alto health care system,palo alto,ca, United States
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Authors
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