SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection
Identifieur interne : 000409 ( Pmc/Curation ); précédent : 000408; suivant : 000410SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection
Auteurs : Nils C. Gassen [Allemagne] ; Daniela Niemeyer [Allemagne] ; Doreen Muth [Allemagne] ; Victor M. Corman [Allemagne] ; Silvia Martinelli [Allemagne] ; Alwine Gassen [Allemagne] ; Kathrin Hafner [Allemagne] ; Jan Papies [Allemagne] ; Kirstin Mösbauer [Allemagne] ; Andreas Zellner [Allemagne] ; Anthony S. Zannas [Allemagne, États-Unis] ; Alexander Herrmann [Allemagne] ; Florian Holsboer [Allemagne] ; Ruth Brack-Werner [Allemagne] ; Michael Boshart [Allemagne] ; Bertram Müller-Myhsok [Allemagne, Royaume-Uni] ; Christian Drosten [Allemagne] ; Marcel A. Müller [Allemagne, Russie] ; Theo Rein [Allemagne]Source :
- Nature Communications [ 2041-1723 ] ; 2019.
Abstract
Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.
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DOI: 10.1038/s41467-019-13659-4
PubMed: 31852899
PubMed Central: 6920372
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Gassen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2240 3300</institution-id><institution-id institution-id-type="GRID">grid.10388.32</institution-id><institution>Department of Psychiatry and Psychotherapy,</institution><institution>University of Bonn,</institution></institution-wrap>Venusberg Campus 1, 53127 Bonn, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Venusberg Campus 1, 53127 Bonn</wicri:regionArea></affiliation></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">German Centre for Infection Research (DZIF), Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research (DZIF), Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">German Centre for Infection Research (DZIF), Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research (DZIF), Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Corman, Victor M" sort="Corman, Victor M" uniqKey="Corman V" first="Victor M." last="Corman">Victor M. Corman</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">German Centre for Infection Research (DZIF), Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research (DZIF), Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Martinelli, Silvia" sort="Martinelli, Silvia" uniqKey="Martinelli S" first="Silvia" last="Martinelli">Silvia Martinelli</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation></author><author><name sortKey="Gassen, Alwine" sort="Gassen, Alwine" uniqKey="Gassen A" first="Alwine" last="Gassen">Alwine Gassen</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 973X</institution-id><institution-id institution-id-type="GRID">grid.5252.0</institution-id><institution>Faculty of Biology, Genetics,</institution><institution>Ludwig-Maximilian-University Munich (LMU),</institution></institution-wrap>82152 Martinsried, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>82152 Martinsried</wicri:regionArea></affiliation></author><author><name sortKey="Hafner, Kathrin" sort="Hafner, Kathrin" uniqKey="Hafner K" first="Kathrin" last="Hafner">Kathrin Hafner</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation></author><author><name sortKey="Papies, Jan" sort="Papies, Jan" uniqKey="Papies J" first="Jan" last="Papies">Jan Papies</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">German Centre for Infection Research (DZIF), Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research (DZIF), Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Mosbauer, Kirstin" sort="Mosbauer, Kirstin" uniqKey="Mosbauer K" first="Kirstin" last="Mösbauer">Kirstin Mösbauer</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">German Centre for Infection Research (DZIF), Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research (DZIF), Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Zellner, Andreas" sort="Zellner, Andreas" uniqKey="Zellner A" first="Andreas" last="Zellner">Andreas Zellner</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation></author><author><name sortKey="Zannas, Anthony S" sort="Zannas, Anthony S" uniqKey="Zannas A" first="Anthony S." last="Zannas">Anthony S. Zannas</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000000100241216</institution-id><institution-id institution-id-type="GRID">grid.189509.c</institution-id><institution>Department of Psychiatry and Behavioral Sciences,</institution><institution>Duke University Medical Center,</institution></institution-wrap>Durham, NC 27710 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Durham</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution>Department of Psychiatry,</institution><institution>University of North Carolina at Chapel Hill,</institution></institution-wrap>438 Taylor Hall, 109 Mason Farm Road, Chapel Hill, 27599-7096 NC USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:regionArea>438 Taylor Hall, 109 Mason Farm Road, Chapel Hill</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 1034 1720</institution-id><institution-id institution-id-type="GRID">grid.410711.2</institution-id><institution>Department of Genetics,</institution><institution>University of North Carolina at Chapel Hil,</institution></institution-wrap>Chapel Hill, 27599 NC USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:regionArea>Chapel Hill</wicri:regionArea></affiliation></author><author><name sortKey="Herrmann, Alexander" sort="Herrmann, Alexander" uniqKey="Herrmann A" first="Alexander" last="Herrmann">Alexander Herrmann</name><affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0483 2525</institution-id><institution-id institution-id-type="GRID">grid.4567.0</institution-id><institution>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health,</institution></institution-wrap>Ingolstädter Landstr. 1, 85764 Neuherberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Ingolstädter Landstr. 1, 85764 Neuherberg</wicri:regionArea></affiliation></author><author><name sortKey="Holsboer, Florian" sort="Holsboer, Florian" uniqKey="Holsboer F" first="Florian" last="Holsboer">Florian Holsboer</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation></author><author><name sortKey="Brack Werner, Ruth" sort="Brack Werner, Ruth" uniqKey="Brack Werner R" first="Ruth" last="Brack-Werner">Ruth Brack-Werner</name><affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0483 2525</institution-id><institution-id institution-id-type="GRID">grid.4567.0</institution-id><institution>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health,</institution></institution-wrap>Ingolstädter Landstr. 1, 85764 Neuherberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Ingolstädter Landstr. 1, 85764 Neuherberg</wicri:regionArea></affiliation></author><author><name sortKey="Boshart, Michael" sort="Boshart, Michael" uniqKey="Boshart M" first="Michael" last="Boshart">Michael Boshart</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 973X</institution-id><institution-id institution-id-type="GRID">grid.5252.0</institution-id><institution>Faculty of Biology, Genetics,</institution><institution>Ludwig-Maximilian-University Munich (LMU),</institution></institution-wrap>82152 Martinsried, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>82152 Martinsried</wicri:regionArea></affiliation></author><author><name sortKey="Muller Myhsok, Bertram" sort="Muller Myhsok, Bertram" uniqKey="Muller Myhsok B" first="Bertram" last="Müller-Myhsok">Bertram Müller-Myhsok</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8470</institution-id><institution-id institution-id-type="GRID">grid.10025.36</institution-id><institution>Institute of Translational Medicine, University of Liverpool,</institution></institution-wrap>L69 3BX Liverpool, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>L69 3BX Liverpool</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="GRID">grid.452617.3</institution-id><institution>Munich Cluster for Systems Neurology - SYNERGY,</institution></institution-wrap>Feodor-Lynen-Str. 17, 81377 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Feodor-Lynen-Str. 17, 81377 Munich</wicri:regionArea></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">German Centre for Infection Research (DZIF), Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research (DZIF), Berlin</wicri:regionArea></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">German Centre for Infection Research (DZIF), Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Infection Research (DZIF), Berlin</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff12"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2288 8774</institution-id><institution-id institution-id-type="GRID">grid.448878.f</institution-id><institution>Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases,</institution><institution>Sechenov University,</institution></institution-wrap>2-4 Bolshaya Pirogovskaya st., 119991 Moscow, Russia</nlm:aff><country xml:lang="fr">Russie</country><wicri:regionArea>2-4 Bolshaya Pirogovskaya st., 119991 Moscow</wicri:regionArea></affiliation></author><author><name sortKey="Rein, Theo" sort="Rein, Theo" uniqKey="Rein T" first="Theo" last="Rein">Theo Rein</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9497 5095</institution-id><institution-id institution-id-type="GRID">grid.419548.5</institution-id><institution>Department of Translational Research in Psychiatry,</institution><institution>Max Planck Institute of Psychiatry,</institution></institution-wrap>Kraepelinstr. 10, 80804 Munich, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kraepelinstr. 10, 80804 Munich</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff13"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 973X</institution-id><institution-id institution-id-type="GRID">grid.5252.0</institution-id><institution>Faculty of Medicine, Physiological Chemistry,</institution><institution>Ludwig-Maximilian-University Munich (LMU),</institution></institution-wrap>82152 Martinsried, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>82152 Martinsried</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bento, Cf" uniqKey="Bento C">CF Bento</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gassen, Nc" uniqKey="Gassen N">NC Gassen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rein, T" uniqKey="Rein T">T Rein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, B" uniqKey="Levine B">B Levine</name></author><author><name sortKey="Liu, R" uniqKey="Liu R">R Liu</name></author><author><name sortKey="Dong, X" uniqKey="Dong X">X Dong</name></author><author><name sortKey="Zhong, Q" uniqKey="Zhong Q">Q Zhong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Itakura, E" uniqKey="Itakura E">E Itakura</name></author><author><name sortKey="Kishi, C" uniqKey="Kishi C">C Kishi</name></author><author><name sortKey="Inoue, K" uniqKey="Inoue K">K Inoue</name></author><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diao, J" uniqKey="Diao J">J Diao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, W" uniqKey="Huang W">W Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Rc" uniqKey="Wang R">RC Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reidick, C" uniqKey="Reidick C">C Reidick</name></author><author><name sortKey="El, Mf" uniqKey="El M">MF El</name></author><author><name sortKey="Meyer, He" uniqKey="Meyer H">HE Meyer</name></author><author><name sortKey="Stenmark, H" uniqKey="Stenmark H">H Stenmark</name></author><author><name sortKey="Platta, Hw" uniqKey="Platta H">HW Platta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, S" uniqKey="Jin S">S Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boutouja, F" uniqKey="Boutouja F">F Boutouja</name></author><author><name sortKey="Brinkmeier, R" uniqKey="Brinkmeier R">R Brinkmeier</name></author><author><name sortKey="Mastalski, T" uniqKey="Mastalski T">T Mastalski</name></author><author><name sortKey="El, Mf" uniqKey="El M">MF El</name></author><author><name sortKey="Platta, Hw" uniqKey="Platta H">HW Platta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dong, X" uniqKey="Dong X">X Dong</name></author><author><name sortKey="Levine, B" uniqKey="Levine B">B Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knoops, K" uniqKey="Knoops K">K Knoops</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cottam, Em" uniqKey="Cottam E">EM Cottam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prentice, E" uniqKey="Prentice E">E Prentice</name></author><author><name sortKey="Jerome, Wg" uniqKey="Jerome W">WG Jerome</name></author><author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T Yoshimori</name></author><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name></author><author><name sortKey="Denison, Mr" uniqKey="Denison M">MR Denison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cong, Y" uniqKey="Cong Y">Y Cong</name></author><author><name sortKey="Verlhac, P" uniqKey="Verlhac P">P Verlhac</name></author><author><name sortKey="Reggiori, F" uniqKey="Reggiori F">F Reggiori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lundin, A" uniqKey="Lundin A">A Lundin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kindrachuk, J" uniqKey="Kindrachuk J">J Kindrachuk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Yc" uniqKey="Kim Y">YC Kim</name></author><author><name sortKey="Guan, Kl" uniqKey="Guan K">KL Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gosert, R" uniqKey="Gosert R">R Gosert</name></author><author><name sortKey="Kanjanahaluethai, A" uniqKey="Kanjanahaluethai A">A Kanjanahaluethai</name></author><author><name sortKey="Egger, D" uniqKey="Egger D">D Egger</name></author><author><name sortKey="Bienz, K" uniqKey="Bienz K">K Bienz</name></author><author><name sortKey="Baker, Sc" uniqKey="Baker S">SC Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reggiori, F" uniqKey="Reggiori F">F Reggiori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, Z" uniqKey="Zhao Z">Z Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, L" uniqKey="Guo L">L Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, L" uniqKey="Zhu L">L Zhu</name></author><author><name sortKey="Mou, C" uniqKey="Mou C">C Mou</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Lin, J" uniqKey="Lin J">J Lin</name></author><author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Storer, Cl" uniqKey="Storer C">CL Storer</name></author><author><name sortKey="Dickey, Ca" uniqKey="Dickey C">CA Dickey</name></author><author><name sortKey="Galigniana, Md" uniqKey="Galigniana M">MD Galigniana</name></author><author><name sortKey="Rein, T" uniqKey="Rein T">T Rein</name></author><author><name sortKey="Cox, Mb" uniqKey="Cox M">MB Cox</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Los, Gv" uniqKey="Los G">GV Los</name></author><author><name sortKey="Wood, K" uniqKey="Wood K">K Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pei, H" uniqKey="Pei H">H Pei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gassen, Nc" uniqKey="Gassen N">NC Gassen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gassen, Nc" uniqKey="Gassen N">NC Gassen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taipale, M" uniqKey="Taipale M">M Taipale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, Cs" uniqKey="Shi C">CS Shi</name></author><author><name sortKey="Kehrl, Jh" uniqKey="Kehrl J">JH Kehrl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akiyama, T" uniqKey="Akiyama T">T Akiyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shin, Hj" uniqKey="Shin H">HJ Shin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ikeda, F" uniqKey="Ikeda F">F Ikeda</name></author><author><name sortKey="Dikic, I" uniqKey="Dikic I">I Dikic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, T" uniqKey="Chen T">T Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, D" uniqKey="Gao D">D Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sierecki, E" uniqKey="Sierecki E">E Sierecki</name></author><author><name sortKey="Sinko, W" uniqKey="Sinko W">W Sinko</name></author><author><name sortKey="Mccammon, Ja" uniqKey="Mccammon J">JA McCammon</name></author><author><name sortKey="Newton, Ac" uniqKey="Newton A">AC Newton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klionsky, Dj" uniqKey="Klionsky D">DJ Klionsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rico Bautista, E" uniqKey="Rico Bautista E">E Rico-Bautista</name></author><author><name sortKey="Yang, Cc" uniqKey="Yang C">CC Yang</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L Lu</name></author><author><name sortKey="Roth, Gp" uniqKey="Roth G">GP Roth</name></author><author><name sortKey="Wolf, Da" uniqKey="Wolf D">DA Wolf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, L" uniqKey="Wu L">L Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aghajanyy, M" uniqKey="Aghajanyy M">M Aghajanyy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Itakura, E" uniqKey="Itakura E">E Itakura</name></author><author><name sortKey="Kishi Itakura, C" uniqKey="Kishi Itakura C">C Kishi-Itakura</name></author><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cottam, Em" uniqKey="Cottam E">EM Cottam</name></author><author><name sortKey="Whelband, Mc" uniqKey="Whelband M">MC Whelband</name></author><author><name sortKey="Wileman, T" uniqKey="Wileman T">T Wileman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oudshoorn, D" uniqKey="Oudshoorn D">D Oudshoorn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D Niemeyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Orvedahl, A" uniqKey="Orvedahl A">A Orvedahl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shoji Kawata, S" uniqKey="Shoji Kawata S">S Shoji-Kawata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malik, Sa" uniqKey="Malik S">SA Malik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsunaga, K" uniqKey="Matsunaga K">K Matsunaga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Cy" uniqKey="Wu C">CY Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, D" uniqKey="Xu D">D Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, C" uniqKey="Xu C">C Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Cc" uniqKey="Liu C">CC Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Platta, Hw" uniqKey="Platta H">HW Platta</name></author><author><name sortKey="Abrahamsen, H" uniqKey="Abrahamsen H">H Abrahamsen</name></author><author><name sortKey="Thoresen, Sb" uniqKey="Thoresen S">SB Thoresen</name></author><author><name sortKey="Stenmark, H" uniqKey="Stenmark H">H Stenmark</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fimia, Gm" uniqKey="Fimia G">GM Fimia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, J" uniqKey="Jin J">J Jin</name></author><author><name sortKey="Arias, Ee" uniqKey="Arias E">EE Arias</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Harper, Jw" uniqKey="Harper J">JW Harper</name></author><author><name sortKey="Walter, Jc" uniqKey="Walter J">JC Walter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xia, P" uniqKey="Xia P">P Xia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ashkenazi, A" uniqKey="Ashkenazi A">A Ashkenazi</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ambjorn, M" uniqKey="Ambjorn M">M Ambjorn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scobey, T" uniqKey="Scobey T">T Scobey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F Almazán</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skotland, T" uniqKey="Skotland T">T Skotland</name></author><author><name sortKey="Iversen, Tg" uniqKey="Iversen T">TG Iversen</name></author><author><name sortKey="Torgersen, Ml" uniqKey="Torgersen M">ML Torgersen</name></author><author><name sortKey="Sandvig, K" uniqKey="Sandvig K">K Sandvig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Campbell, Gr" uniqKey="Campbell G">GR Campbell</name></author><author><name sortKey="Spector, Sa" uniqKey="Spector S">SA Spector</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Orvedahl, A" uniqKey="Orvedahl A">A Orvedahl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akhrymuk, I" uniqKey="Akhrymuk I">I Akhrymuk</name></author><author><name sortKey="Kulemzin, Sv" uniqKey="Kulemzin S">SV Kulemzin</name></author><author><name sortKey="Frolova, Ei" uniqKey="Frolova E">EI Frolova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Dy" uniqKey="Kim D">DY Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Galluzzi, L" uniqKey="Galluzzi L">L Galluzzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, Tc" uniqKey="Smith T">TC Smith</name></author><author><name sortKey="Kinkel, Aw" uniqKey="Kinkel A">AW Kinkel</name></author><author><name sortKey="Gryczko, Cm" uniqKey="Gryczko C">CM Gryczko</name></author><author><name sortKey="Goulet, Jr" uniqKey="Goulet J">JR Goulet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andrews, P" uniqKey="Andrews P">P Andrews</name></author><author><name sortKey="Thyssen, J" uniqKey="Thyssen J">J Thyssen</name></author><author><name sortKey="Lorke, D" uniqKey="Lorke D">D Lorke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Costabile, G" uniqKey="Costabile G">G Costabile</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rubinsztein, Dc" uniqKey="Rubinsztein D">DC Rubinsztein</name></author><author><name sortKey="Codogno, P" uniqKey="Codogno P">P Codogno</name></author><author><name sortKey="Levine, B" uniqKey="Levine B">B Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rubinsztein, Dc" uniqKey="Rubinsztein D">DC Rubinsztein</name></author><author><name sortKey="Bento, Cf" uniqKey="Bento C">CF Bento</name></author><author><name sortKey="Deretic, V" uniqKey="Deretic V">V Deretic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zschocke, J" uniqKey="Zschocke J">J Zschocke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miracco, C" uniqKey="Miracco C">C Miracco</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byrnes, Ap" uniqKey="Byrnes A">AP Byrnes</name></author><author><name sortKey="Griffin, De" uniqKey="Griffin D">DE Griffin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tischer, Bk" uniqKey="Tischer B">BK Tischer</name></author><author><name sortKey="Smith, Ga" uniqKey="Smith G">GA Smith</name></author><author><name sortKey="Osterrieder, N" uniqKey="Osterrieder N">N Osterrieder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wochnik, Gm" uniqKey="Wochnik G">GM Wochnik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kimura, S" uniqKey="Kimura S">S Kimura</name></author><author><name sortKey="Noda, T" uniqKey="Noda T">T Noda</name></author><author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T Yoshimori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name></author><author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T Yoshimori</name></author><author><name sortKey="Levine, B" uniqKey="Levine B">B Levine</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31852899</article-id><article-id pub-id-type="pmc">6920372</article-id><article-id pub-id-type="publisher-id">13659</article-id><article-id pub-id-type="doi">10.1038/s41467-019-13659-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Gassen</surname><given-names>Nils C.</given-names></name><address><email>ncgassen@psych.mpg.de</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-1897-6365</contrib-id><name><surname>Niemeyer</surname><given-names>Daniela</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Muth</surname><given-names>Doreen</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-3605-0136</contrib-id><name><surname>Corman</surname><given-names>Victor M.</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Martinelli</surname><given-names>Silvia</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gassen</surname><given-names>Alwine</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Hafner</surname><given-names>Kathrin</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Papies</surname><given-names>Jan</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Mösbauer</surname><given-names>Kirstin</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Zellner</surname><given-names>Andreas</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-6897-9652</contrib-id><name><surname>Zannas</surname><given-names>Anthony S.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff6">6</xref><xref ref-type="aff" rid="Aff7">7</xref><xref ref-type="aff" rid="Aff8">8</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-2749-9003</contrib-id><name><surname>Herrmann</surname><given-names>Alexander</given-names></name><xref ref-type="aff" rid="Aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Holsboer</surname><given-names>Florian</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Brack-Werner</surname><given-names>Ruth</given-names></name><xref ref-type="aff" rid="Aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Boshart</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Müller-Myhsok</surname><given-names>Bertram</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff10">10</xref><xref ref-type="aff" rid="Aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Drosten</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-2242-5117</contrib-id><name><surname>Müller</surname><given-names>Marcel A.</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref><xref ref-type="aff" rid="Aff12">12</xref></contrib><contrib contrib-type="author" corresp="yes" 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Psychotherapy,</institution><institution>University of Bonn,</institution></institution-wrap>Venusberg Campus 1, 53127 Bonn, Germany</aff><aff id="Aff3"><label>3</label>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany</aff><aff id="Aff4"><label>4</label>German Centre for Infection Research (DZIF), Berlin, Germany</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 973X</institution-id><institution-id institution-id-type="GRID">grid.5252.0</institution-id><institution>Faculty of Biology, Genetics,</institution><institution>Ludwig-Maximilian-University Munich (LMU),</institution></institution-wrap>82152 Martinsried, Germany</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="ISNI">0000000100241216</institution-id><institution-id 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Hill, 27599 NC USA</aff><aff id="Aff9"><label>9</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0483 2525</institution-id><institution-id institution-id-type="GRID">grid.4567.0</institution-id><institution>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health,</institution></institution-wrap>Ingolstädter Landstr. 1, 85764 Neuherberg, Germany</aff><aff id="Aff10"><label>10</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8470</institution-id><institution-id institution-id-type="GRID">grid.10025.36</institution-id><institution>Institute of Translational Medicine, University of Liverpool,</institution></institution-wrap>L69 3BX Liverpool, UK</aff><aff id="Aff11"><label>11</label><institution-wrap><institution-id institution-id-type="GRID">grid.452617.3</institution-id><institution>Munich Cluster for Systems Neurology - SYNERGY,</institution></institution-wrap>Feodor-Lynen-Str. 17, 81377 Munich, Germany</aff><aff id="Aff12"><label>12</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2288 8774</institution-id><institution-id institution-id-type="GRID">grid.448878.f</institution-id><institution>Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases,</institution><institution>Sechenov University,</institution></institution-wrap>2-4 Bolshaya Pirogovskaya st., 119991 Moscow, Russia</aff><aff id="Aff13"><label>13</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 973X</institution-id><institution-id institution-id-type="GRID">grid.5252.0</institution-id><institution>Faculty of Medicine, Physiological Chemistry,</institution><institution>Ludwig-Maximilian-University Munich (LMU),</institution></institution-wrap>82152 Martinsried, Germany</aff></contrib-group><pub-date pub-type="epub"><day>18</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>18</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>5770</elocation-id><history><date date-type="received"><day>11</day><month>6</month><year>2018</year></date><date date-type="accepted"><day>14</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2019</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">Here, Gassen <italic>et al</italic>. show that S-phase kinase-associated protein 2 (SKP2) is responsible for lysine-48-linked poly-ubiquitination of beclin 1, resulting in its proteasomal degradation, and that inhibition of SKP2 enhances autophagy and reduces replication of MERS coronavirus.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Macroautophagy</kwd><kwd>Antivirals</kwd><kwd>Ubiquitin ligases</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100001659</institution-id><institution>Deutsche Forschungsgemeinschaft (German Research Foundation)</institution></institution-wrap></funding-source><award-id>SPP1596</award-id><award-id>SFB-TR84</award-id><principal-award-recipient><name><surname>Drosten</surname><given-names>Christian</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100010571</institution-id><institution>Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Federal Ministry for Education, Science, Research and Technology)</institution></institution-wrap></funding-source><award-id>APID (#01KI1723A)</award-id><principal-award-recipient><name><surname>Drosten</surname><given-names>Christian</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100010686</institution-id><institution>EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)</institution></institution-wrap></funding-source><award-id>COMPARE (# 643476) and EVAg (#653316)</award-id><principal-award-recipient><name><surname>Drosten</surname><given-names>Christian</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100001663</institution-id><institution>Volkswagen Foundation (VolkswagenStiftung)</institution></institution-wrap></funding-source><award-id>#93345</award-id><principal-award-recipient><name><surname>Müller</surname><given-names>Marcel A.</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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