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Article: OTUB1 is a key regulator of RIG-I-dependent immune signaling and is targeted for proteasomal degradation by influenza A NS1

TitleOTUB1 is a key regulator of RIG-I-dependent immune signaling and is targeted for proteasomal degradation by influenza A NS1
Authors
Keywordsdeubiquitylases
RIG-I signaling
ubiquitylation
innate immune response
RNA virus
Issue Date2020
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports
Citation
Cell Reports, 2020, v. 30 n. 5, p. 1570-1584 How to Cite?
AbstractDeubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [35S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses.
Persistent Identifierhttp://hdl.handle.net/10722/287238
ISSN
2020 Impact Factor: 9.423
2020 SCImago Journal Rankings: 6.264
ISI Accession Number ID
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DC FieldValueLanguage
dc.contributor.authorAkhee, SJ-
dc.contributor.authorBiquand, E-
dc.contributor.authorMunoz-Moreno, R-
dc.contributor.authorLe Quang, A-
dc.contributor.authorMok, CKP-
dc.contributor.authorWong, HH-
dc.contributor.authorTEO, QW-
dc.contributor.authorDoak, SA-
dc.contributor.authorChin, AWH-
dc.contributor.authorPoon, LML-
dc.contributor.authorTe Velthuis, A-
dc.contributor.authorGarcia-Sastre, A-
dc.contributor.authorDemeret, C-
dc.contributor.authorSanyal, S-
dc.date.accessioned2020-09-22T02:57:56Z-
dc.date.available2020-09-22T02:57:56Z-
dc.date.issued2020-
dc.identifier.citationCell Reports, 2020, v. 30 n. 5, p. 1570-1584-
dc.identifier.issn2211-1247-
dc.identifier.urihttp://hdl.handle.net/10722/287238-
dc.description.abstractDeubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [35S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports-
dc.relation.ispartofCell Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectdeubiquitylases-
dc.subjectRIG-I signaling-
dc.subjectubiquitylation-
dc.subjectinnate immune response-
dc.subjectRNA virus-
dc.titleOTUB1 is a key regulator of RIG-I-dependent immune signaling and is targeted for proteasomal degradation by influenza A NS1-
dc.typeArticle-
dc.identifier.emailMok, CKP: ch02mkp@hkucc.hku.hk-
dc.identifier.emailDoak, SA: sophiev@hku.hk-
dc.identifier.emailChin, AWH: alexchin@hku.hk-
dc.identifier.emailPoon, LML: llmpoon@hkucc.hku.hk-
dc.identifier.emailSanyal, S: sanyal@hku.hk-
dc.identifier.authorityMok, CKP=rp01805-
dc.identifier.authorityDoak, SA=rp02141-
dc.identifier.authorityChin, AWH=rp02345-
dc.identifier.authorityPoon, LML=rp00484-
dc.identifier.authoritySanyal, S=rp01794-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.celrep.2020.01.015-
dc.identifier.pmid32023470-
dc.identifier.scopuseid_2-s2.0-85078802699-
dc.identifier.hkuros314276-
dc.identifier.volume30-
dc.identifier.issue5-
dc.identifier.spage1570-
dc.identifier.epage1584-
dc.identifier.isiWOS:000511294400024-
dc.publisher.placeUnited States-
dc.relation.projectMechanism of OtuB1-mediated regulation in influenza virus infection-
dc.identifier.issnl2211-1247-

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