MersV1, PubMed, Curation, bibRecord, 000324

SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection.

Identifieur interne : 000324 ( PubMed/Curation ); précédent : 000323; suivant : 000325

SKP2 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] ; Alexander Herrmann [Allemagne] ; Florian Holsboer [Allemagne] ; Ruth Brack-Werner [Allemagne] ; Michael Boshart [Allemagne] ; Bertram Müller-Myhsok [Allemagne] ; Christian Drosten [Allemagne] ; Marcel A. Müller [Allemagne] ; Theo Rein [Allemagne]

Source :

Nature communications [ 2041-1723 ] ; 2019.

RBID : pubmed:31852899

Descripteurs français

KwdFr :
- Animaux, Autophagie (), Autophagie (immunologie), Bécline-1 (métabolisme), Cellules HEK293, Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Humains, Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Protéines associées aux kinases de la phase S (antagonistes et inhibiteurs), Protéines associées aux kinases de la phase S (génétique), Protéines associées aux kinases de la phase S (métabolisme), Protéolyse (), Techniques de knock-down de gènes, Ubiquitinylation (), Ubiquitinylation (immunologie).
MESH :
- antagonistes et inhibiteurs : Protéines associées aux kinases de la phase S.
- génétique : Protéines associées aux kinases de la phase S.
- immunologie : Autophagie, Coronavirus du syndrome respiratoire du Moyen-Orient, Infections à coronavirus, Ubiquitinylation.
- métabolisme : Bécline-1, Protéines associées aux kinases de la phase S.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus.
- Animaux, Autophagie, Cellules HEK293, Cellules Vero, Humains, Protéolyse, Techniques de knock-down de gènes, Ubiquitinylation.

English descriptors

KwdEn :
- Animals, Autophagy (drug effects), Autophagy (immunology), Beclin-1 (metabolism), Chlorocebus aethiops, Coronavirus Infections (immunology), Coronavirus Infections (virology), Gene Knockdown Techniques, HEK293 Cells, Humans, Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Proteolysis (drug effects), S-Phase Kinase-Associated Proteins (antagonists & inhibitors), S-Phase Kinase-Associated Proteins (genetics), S-Phase Kinase-Associated Proteins (metabolism), Ubiquitination (drug effects), Ubiquitination (immunology), Vero Cells.
MESH :
- chemical , antagonists & inhibitors : S-Phase Kinase-Associated Proteins.
- chemical , genetics : S-Phase Kinase-Associated Proteins.
- chemical , metabolism : Beclin-1, S-Phase Kinase-Associated Proteins.
- drug effects : Autophagy, Proteolysis, Ubiquitination.
- immunology : Autophagy, Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus, Ubiquitination.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections.
- Animals, Chlorocebus aethiops, Gene Knockdown Techniques, HEK293 Cells, Humans, Vero Cells.

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.

DOI: 10.1038/s41467-019-13659-4
PubMed: 31852899

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<author><name sortKey="Brack Werner, Ruth" sort="Brack Werner, Ruth" uniqKey="Brack Werner R" first="Ruth" last="Brack-Werner">Ruth Brack-Werner</name>
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<author><name sortKey="Boshart, Michael" sort="Boshart, Michael" uniqKey="Boshart M" first="Michael" last="Boshart">Michael Boshart</name>
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<author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Corman, Victor M" sort="Corman, Victor M" uniqKey="Corman V" first="Victor M" last="Corman">Victor M. Corman</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Martinelli, Silvia" sort="Martinelli, Silvia" uniqKey="Martinelli S" first="Silvia" last="Martinelli">Silvia Martinelli</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich</wicri:regionArea>
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<author><name sortKey="Gassen, Alwine" sort="Gassen, Alwine" uniqKey="Gassen A" first="Alwine" last="Gassen">Alwine Gassen</name>
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<author><name sortKey="Hafner, Kathrin" sort="Hafner, Kathrin" uniqKey="Hafner K" first="Kathrin" last="Hafner">Kathrin Hafner</name>
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<author><name sortKey="Papies, Jan" sort="Papies, Jan" uniqKey="Papies J" first="Jan" last="Papies">Jan Papies</name>
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<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>
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<author><name sortKey="Mosbauer, Kirstin" sort="Mosbauer, Kirstin" uniqKey="Mosbauer K" first="Kirstin" last="Mösbauer">Kirstin Mösbauer</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Zellner, Andreas" sort="Zellner, Andreas" uniqKey="Zellner A" first="Andreas" last="Zellner">Andreas Zellner</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Zannas, Anthony S" sort="Zannas, Anthony S" uniqKey="Zannas A" first="Anthony S" last="Zannas">Anthony S. Zannas</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich</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:affiliation>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health, 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>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 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:affiliation>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health, 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:affiliation>Faculty of Biology, Genetics, Ludwig-Maximilian-University Munich (LMU), 82152, Martinsried, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<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:affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Rein, Theo" sort="Rein, Theo" uniqKey="Rein T" first="Theo" last="Rein">Theo Rein</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany. theorein@psych.mpg.de.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
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<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2019" type="published">2019</date>
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<term>Autophagy (drug effects)</term>
<term>Autophagy (immunology)</term>
<term>Beclin-1 (metabolism)</term>
<term>Chlorocebus aethiops</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Gene Knockdown Techniques</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term>
<term>Proteolysis (drug effects)</term>
<term>S-Phase Kinase-Associated Proteins (antagonists & inhibitors)</term>
<term>S-Phase Kinase-Associated Proteins (genetics)</term>
<term>S-Phase Kinase-Associated Proteins (metabolism)</term>
<term>Ubiquitination (drug effects)</term>
<term>Ubiquitination (immunology)</term>
<term>Vero Cells</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Autophagie ()</term>
<term>Autophagie (immunologie)</term>
<term>Bécline-1 (métabolisme)</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term>
<term>Humains</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Protéines associées aux kinases de la phase S (antagonistes et inhibiteurs)</term>
<term>Protéines associées aux kinases de la phase S (génétique)</term>
<term>Protéines associées aux kinases de la phase S (métabolisme)</term>
<term>Protéolyse ()</term>
<term>Techniques de knock-down de gènes</term>
<term>Ubiquitinylation ()</term>
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<term>S-Phase Kinase-Associated Proteins</term>
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<term>Proteolysis</term>
<term>Ubiquitination</term>
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</keywords>
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<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Infections à coronavirus</term>
<term>Ubiquitinylation</term>
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<term>Coronavirus Infections</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Ubiquitination</term>
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<term>Chlorocebus aethiops</term>
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<term>Autophagie</term>
<term>Cellules HEK293</term>
<term>Cellules Vero</term>
<term>Humains</term>
<term>Protéolyse</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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<DateCompleted><Year>2020</Year>
<Month>04</Month>
<Day>02</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>04</Month>
<Day>02</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>10</Volume>
<Issue>1</Issue>
<PubDate><Year>2019</Year>
<Month>12</Month>
<Day>18</Day>
</PubDate>
</JournalIssue>
<Title>Nature communications</Title>
<ISOAbbreviation>Nat Commun</ISOAbbreviation>
</Journal>
<ArticleTitle>SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection.</ArticleTitle>
<Pagination><MedlinePgn>5770</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-019-13659-4</ELocationID>
<Abstract><AbstractText>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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gassen</LastName>
<ForeName>Nils C</ForeName>
<Initials>NC</Initials>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany. ncgassen@psych.mpg.de.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Psychiatry and Psychotherapy, University of Bonn, Venusberg Campus 1, 53127, Bonn, Germany. ncgassen@psych.mpg.de.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Niemeyer</LastName>
<ForeName>Daniela</ForeName>
<Initials>D</Initials>
<Identifier Source="ORCID">0000-0002-1897-6365</Identifier>
<AffiliationInfo><Affiliation>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Centre for Infection Research (DZIF), Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Muth</LastName>
<ForeName>Doreen</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Centre for Infection Research (DZIF), Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Corman</LastName>
<ForeName>Victor M</ForeName>
<Initials>VM</Initials>
<Identifier Source="ORCID">0000-0002-3605-0136</Identifier>
<AffiliationInfo><Affiliation>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Centre for Infection Research (DZIF), Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Martinelli</LastName>
<ForeName>Silvia</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gassen</LastName>
<ForeName>Alwine</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Faculty of Biology, Genetics, Ludwig-Maximilian-University Munich (LMU), 82152, Martinsried, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hafner</LastName>
<ForeName>Kathrin</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Papies</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Centre for Infection Research (DZIF), Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mösbauer</LastName>
<ForeName>Kirstin</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Centre for Infection Research (DZIF), Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zellner</LastName>
<ForeName>Andreas</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zannas</LastName>
<ForeName>Anthony S</ForeName>
<Initials>AS</Initials>
<Identifier Source="ORCID">0000-0002-6897-9652</Identifier>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27710, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Psychiatry, University of North Carolina at Chapel Hill, 438 Taylor Hall, 109 Mason Farm Road, Chapel Hill, 27599-7096, NC, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Genetics, University of North Carolina at Chapel Hil, Chapel Hill, 27599, NC, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Herrmann</LastName>
<ForeName>Alexander</ForeName>
<Initials>A</Initials>
<Identifier Source="ORCID">0000-0002-2749-9003</Identifier>
<AffiliationInfo><Affiliation>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Holsboer</LastName>
<ForeName>Florian</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brack-Werner</LastName>
<ForeName>Ruth</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>HIV-Cell-Interactions Group, Institute of Virology, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Boshart</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Faculty of Biology, Genetics, Ludwig-Maximilian-University Munich (LMU), 82152, Martinsried, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Müller-Myhsok</LastName>
<ForeName>Bertram</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Translational Medicine, University of Liverpool, L69 3BX, Liverpool, UK.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Munich Cluster for Systems Neurology - SYNERGY, Feodor-Lynen-Str. 17, 81377, Munich, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Drosten</LastName>
<ForeName>Christian</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Centre for Infection Research (DZIF), Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Müller</LastName>
<ForeName>Marcel A</ForeName>
<Initials>MA</Initials>
<Identifier Source="ORCID">0000-0003-2242-5117</Identifier>
<AffiliationInfo><Affiliation>Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Centre for Infection Research (DZIF), Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, 2-4 Bolshaya Pirogovskaya st., 119991, Moscow, Russia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rein</LastName>
<ForeName>Theo</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">0000-0003-2850-4289</Identifier>
<AffiliationInfo><Affiliation>Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany. theorein@psych.mpg.de.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Faculty of Medicine, Physiological Chemistry, Ludwig-Maximilian-University Munich (LMU), 82152, Martinsried, Germany. theorein@psych.mpg.de.</Affiliation>
</AffiliationInfo>
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<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>12</Month>
<Day>18</Day>
</ArticleDate>
</Article>
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<MedlineTA>Nat Commun</MedlineTA>
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<NameOfSubstance UI="C491997">BECN1 protein, human</NameOfSubstance>
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<NameOfSubstance UI="D000071186">Beclin-1</NameOfSubstance>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
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<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055785" MajorTopicYN="N">Gene Knockdown Techniques</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
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<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059748" MajorTopicYN="N">Proteolysis</DescriptorName>
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</MeshHeading>
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<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054875" MajorTopicYN="N">Ubiquitination</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year>
<Month>06</Month>
<Day>11</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2019</Year>
<Month>11</Month>
<Day>14</Day>
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SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection.

SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection.

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