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dc.contributor.authorStubbe, Miona
dc.contributor.authorMai, Julia
dc.contributor.authorPaulus, Christina
dc.contributor.authorStubbe, Hans Christian
dc.contributor.authorBerscheminski, Julia
dc.contributor.authorKarimi, Maryam
dc.contributor.authorHofmann, Samuel
dc.contributor.authorWeber, Elisabeth
dc.contributor.authorHadian, Kamyar
dc.contributor.authorHay, Ron
dc.contributor.authorGroitl, Peter
dc.contributor.authorNevels, Michael
dc.contributor.authorDobner, Thomas
dc.contributor.authorSchreiner, Sabrina
dc.date.accessioned2020-04-02T15:30:06Z
dc.date.available2020-04-02T15:30:06Z
dc.date.issued2020-03
dc.identifier.citationStubbe , M , Mai , J , Paulus , C , Stubbe , H C , Berscheminski , J , Karimi , M , Hofmann , S , Weber , E , Hadian , K , Hay , R , Groitl , P , Nevels , M , Dobner , T & Schreiner , S 2020 , ' Viral DNA binding protein SUMOylation promotes PML nuclear body localization next to viral replication centers ' , mBio , vol. 11 , no. 2 , e00049-20 . https://doi.org/10.1128/mBio.00049-20en
dc.identifier.issn2150-7511
dc.identifier.otherPURE: 267190056
dc.identifier.otherPURE UUID: d625b34f-1cd1-4d90-a0a1-fc275973d2ac
dc.identifier.otherScopus: 85082038604
dc.identifier.otherPubMed: 32184235
dc.identifier.otherORCID: /0000-0002-7115-407X/work/71559970
dc.identifier.otherORCID: /0000-0002-4123-5629/work/71559991
dc.identifier.otherWOS: 000531071300121
dc.identifier.urihttps://hdl.handle.net/10023/19747
dc.descriptionWe thank Kenji Schorpp (Munich, Germany) for support with our yeast work and Roger Everett (Glasgow, United Kingdom) for reagents. We greatly appreciate the scientific discussion with Michelle Vincendeau, Ruth Brack-Werner, and Ulrike Protzer. This work was supported by the Dräger Stiftung eV, the Deutsche Krebshilfe eV, and the Deutsche Forschungsgemeinschaft (DFG TRR179 P16).en
dc.description.abstractHuman adenoviruses (HAdVs) have developed mechanisms to manipulate cellular antiviral measures to ensure proper DNA replication, with detailed processes far from being understood. Host cells repress incoming viral genomes through a network of transcriptional regulators that normally control cellular homeostasis. The nuclear domains involved are promyelocytic leukemia protein nuclear bodies (PML-NBs), interferon-inducible, dot-like nuclear structures and hot spots of SUMO posttranslational modification (PTM). In HAdV-infected cells, such SUMO factories are found in close proximity to newly established viral replication centers (RCs) marked by the adenoviral DNA binding protein (DBP) E2A. Here, we show that E2A is a novel target of host SUMOylation, leading to PTMs supporting E2A function in promoting productive infection. Our data show that SUMOylated E2A interacts with PML. Decreasing SUMO-E2A protein levels by generating HAdV variants mutated in the three main SUMO conjugation motifs (SCMs) led to lower numbers of viral RCs and PML-NBs, and these two structures were no longer next to each other. Our data further indicate that SUMOylated E2A binds the host transcription factor Sp100A, promoting HAdV gene expression, and represents the molecular bridge between PML tracks and adjacent viral RCs. Consequently, E2A SCM mutations repressed late viral gene expression and progeny production. These data highlight a novel mechanism used by the virus to benefit from host antiviral responses by exploiting the cellular SUMO conjugation machinery.
dc.format.extent21
dc.language.isoeng
dc.relation.ispartofmBioen
dc.rightsCopyright © 2020 Stubbe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en
dc.subjectDNA binding proteinen
dc.subjectE2A/DBPen
dc.subjectHAdVen
dc.subjectHuman adenovirusen
dc.subjectPML-NBen
dc.subjectReplication centersen
dc.subjectSp100en
dc.subjectSUMOen
dc.subjectTranscriptionen
dc.subjectVirusen
dc.subjectQH301 Biologyen
dc.subjectQR355 Virologyen
dc.subjectMicrobiologyen
dc.subjectVirologyen
dc.subjectDASen
dc.subject.lccQH301en
dc.subject.lccQR355en
dc.titleViral DNA binding protein SUMOylation promotes PML nuclear body localization next to viral replication centersen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1128/mBio.00049-20
dc.description.statusPeer revieweden


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