CovidV1, Main, Exploration, bibRecord, 000B63

Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells

Identifieur interne : 000B63 ( Main/Exploration ); précédent : 000B62; suivant : 000B64

Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells

Auteurs : Giovanna Clavarino [France] ; Nuno Cláudio [France] ; Alexandre Dalet [France] ; Seigo Terawaki [France] ; Thérèse Couderc [France] ; Lionel Chasson [France] ; Maurizio Ceppi [France] ; Enrico K. Schmidt [France] ; Till Wenger [France] ; Marc Lecuit [France] ; Evelina Gatti [France] ; Philippe Pierre [France]

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2012.

RBID : PMC:3286954

Abstract

In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (pI:C), DCs mount a specific integrated stress response during which the transcription factor ATF4 and the growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), a phosphatase 1 (PP1) cofactor, are expressed. In agreement with increased GADD34 levels, an extensive dephosphorylation of the translation initiation factor eIF2α was observed during DC activation. Unexpectedly, although DCs display an unusual resistance to protein synthesis inhibition induced in response to cytosolic dsRNA, GADD34 expression did not have a major impact on protein synthesis. GADD34, however, was shown to be required for normal cytokine production both in vitro and in vivo. These observations have important implications in linking further pathogen detection with the integrated stress response pathways.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286954

DOI: 10.1073/pnas.1104491109
PubMed: 22315398
PubMed Central: 3286954

Affiliations:

France

Le document en format XML

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</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institut National de la Santé et de la Recherche Médicale</institution>
 (INSERM), U631, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Centre National de la Recherche Scientifique</institution>
, Unité Mixte de Recherche 6102, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ceppi, Maurizio" sort="Ceppi, Maurizio" uniqKey="Ceppi M" first="Maurizio" last="Ceppi">Maurizio Ceppi</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Centre d'Immunologie de Marseille-Luminy,<institution>Aix-Marseille University</institution>
, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institut National de la Santé et de la Recherche Médicale</institution>
 (INSERM), U631, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Centre National de la Recherche Scientifique</institution>
, Unité Mixte de Recherche 6102, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Schmidt, Enrico K" sort="Schmidt, Enrico K" uniqKey="Schmidt E" first="Enrico K." last="Schmidt">Enrico K. Schmidt</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Centre d'Immunologie de Marseille-Luminy,<institution>Aix-Marseille University</institution>
, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institut National de la Santé et de la Recherche Médicale</institution>
 (INSERM), U631, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Centre National de la Recherche Scientifique</institution>
, Unité Mixte de Recherche 6102, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wenger, Till" sort="Wenger, Till" uniqKey="Wenger T" first="Till" last="Wenger">Till Wenger</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Centre d'Immunologie de Marseille-Luminy,<institution>Aix-Marseille University</institution>
, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institut National de la Santé et de la Recherche Médicale</institution>
 (INSERM), U631, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Centre National de la Recherche Scientifique</institution>
, Unité Mixte de Recherche 6102, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lecuit, Marc" sort="Lecuit, Marc" uniqKey="Lecuit M" first="Marc" last="Lecuit">Marc Lecuit</name>
<affiliation wicri:level="1"><nlm:aff id="aff4">Microbes and Host Barriers Group,<institution>Institut Pasteur</institution>
, 75015 Paris,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff5"><institution>INSERM</institution>
, Equipe avenir U604, 75015 Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6">Service des Maladies Infectieuses et Tropicales,<institution>Université Paris Descartes, Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris</institution>
, 75015 Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gatti, Evelina" sort="Gatti, Evelina" uniqKey="Gatti E" first="Evelina" last="Gatti">Evelina Gatti</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Centre d'Immunologie de Marseille-Luminy,<institution>Aix-Marseille University</institution>
, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institut National de la Santé et de la Recherche Médicale</institution>
 (INSERM), U631, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Centre National de la Recherche Scientifique</institution>
, Unité Mixte de Recherche 6102, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pierre, Philippe" sort="Pierre, Philippe" uniqKey="Pierre P" first="Philippe" last="Pierre">Philippe Pierre</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Centre d'Immunologie de Marseille-Luminy,<institution>Aix-Marseille University</institution>
, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institut National de la Santé et de la Recherche Médicale</institution>
 (INSERM), U631, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Centre National de la Recherche Scientifique</institution>
, Unité Mixte de Recherche 6102, 13288 Marseille,<country>France</country>
;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (pI:C), DCs mount a specific integrated stress response during which the transcription factor ATF4 and the growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), a phosphatase 1 (PP1) cofactor, are expressed. In agreement with increased GADD34 levels, an extensive dephosphorylation of the translation initiation factor eIF2α was observed during DC activation. Unexpectedly, although DCs display an unusual resistance to protein synthesis inhibition induced in response to cytosolic dsRNA, GADD34 expression did not have a major impact on protein synthesis. GADD34, however, was shown to be required for normal cytokine production both in vitro and in vivo. These observations have important implications in linking further pathogen detection with the integrated stress response pathways.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
</country>
</list>
<tree><country name="France"><noRegion><name sortKey="Clavarino, Giovanna" sort="Clavarino, Giovanna" uniqKey="Clavarino G" first="Giovanna" last="Clavarino">Giovanna Clavarino</name>
</noRegion>
<name sortKey="Ceppi, Maurizio" sort="Ceppi, Maurizio" uniqKey="Ceppi M" first="Maurizio" last="Ceppi">Maurizio Ceppi</name>
<name sortKey="Ceppi, Maurizio" sort="Ceppi, Maurizio" uniqKey="Ceppi M" first="Maurizio" last="Ceppi">Maurizio Ceppi</name>
<name sortKey="Ceppi, Maurizio" sort="Ceppi, Maurizio" uniqKey="Ceppi M" first="Maurizio" last="Ceppi">Maurizio Ceppi</name>
<name sortKey="Chasson, Lionel" sort="Chasson, Lionel" uniqKey="Chasson L" first="Lionel" last="Chasson">Lionel Chasson</name>
<name sortKey="Chasson, Lionel" sort="Chasson, Lionel" uniqKey="Chasson L" first="Lionel" last="Chasson">Lionel Chasson</name>
<name sortKey="Chasson, Lionel" sort="Chasson, Lionel" uniqKey="Chasson L" first="Lionel" last="Chasson">Lionel Chasson</name>
<name sortKey="Claudio, Nuno" sort="Claudio, Nuno" uniqKey="Claudio N" first="Nuno" last="Cláudio">Nuno Cláudio</name>
<name sortKey="Claudio, Nuno" sort="Claudio, Nuno" uniqKey="Claudio N" first="Nuno" last="Cláudio">Nuno Cláudio</name>
<name sortKey="Claudio, Nuno" sort="Claudio, Nuno" uniqKey="Claudio N" first="Nuno" last="Cláudio">Nuno Cláudio</name>
<name sortKey="Clavarino, Giovanna" sort="Clavarino, Giovanna" uniqKey="Clavarino G" first="Giovanna" last="Clavarino">Giovanna Clavarino</name>
<name sortKey="Clavarino, Giovanna" sort="Clavarino, Giovanna" uniqKey="Clavarino G" first="Giovanna" last="Clavarino">Giovanna Clavarino</name>
<name sortKey="Couderc, Therese" sort="Couderc, Therese" uniqKey="Couderc T" first="Thérèse" last="Couderc">Thérèse Couderc</name>
<name sortKey="Couderc, Therese" sort="Couderc, Therese" uniqKey="Couderc T" first="Thérèse" last="Couderc">Thérèse Couderc</name>
<name sortKey="Dalet, Alexandre" sort="Dalet, Alexandre" uniqKey="Dalet A" first="Alexandre" last="Dalet">Alexandre Dalet</name>
<name sortKey="Dalet, Alexandre" sort="Dalet, Alexandre" uniqKey="Dalet A" first="Alexandre" last="Dalet">Alexandre Dalet</name>
<name sortKey="Dalet, Alexandre" sort="Dalet, Alexandre" uniqKey="Dalet A" first="Alexandre" last="Dalet">Alexandre Dalet</name>
<name sortKey="Gatti, Evelina" sort="Gatti, Evelina" uniqKey="Gatti E" first="Evelina" last="Gatti">Evelina Gatti</name>
<name sortKey="Gatti, Evelina" sort="Gatti, Evelina" uniqKey="Gatti E" first="Evelina" last="Gatti">Evelina Gatti</name>
<name sortKey="Gatti, Evelina" sort="Gatti, Evelina" uniqKey="Gatti E" first="Evelina" last="Gatti">Evelina Gatti</name>
<name sortKey="Lecuit, Marc" sort="Lecuit, Marc" uniqKey="Lecuit M" first="Marc" last="Lecuit">Marc Lecuit</name>
<name sortKey="Lecuit, Marc" sort="Lecuit, Marc" uniqKey="Lecuit M" first="Marc" last="Lecuit">Marc Lecuit</name>
<name sortKey="Lecuit, Marc" sort="Lecuit, Marc" uniqKey="Lecuit M" first="Marc" last="Lecuit">Marc Lecuit</name>
<name sortKey="Pierre, Philippe" sort="Pierre, Philippe" uniqKey="Pierre P" first="Philippe" last="Pierre">Philippe Pierre</name>
<name sortKey="Pierre, Philippe" sort="Pierre, Philippe" uniqKey="Pierre P" first="Philippe" last="Pierre">Philippe Pierre</name>
<name sortKey="Pierre, Philippe" sort="Pierre, Philippe" uniqKey="Pierre P" first="Philippe" last="Pierre">Philippe Pierre</name>
<name sortKey="Schmidt, Enrico K" sort="Schmidt, Enrico K" uniqKey="Schmidt E" first="Enrico K." last="Schmidt">Enrico K. Schmidt</name>
<name sortKey="Schmidt, Enrico K" sort="Schmidt, Enrico K" uniqKey="Schmidt E" first="Enrico K." last="Schmidt">Enrico K. Schmidt</name>
<name sortKey="Schmidt, Enrico K" sort="Schmidt, Enrico K" uniqKey="Schmidt E" first="Enrico K." last="Schmidt">Enrico K. Schmidt</name>
<name sortKey="Terawaki, Seigo" sort="Terawaki, Seigo" uniqKey="Terawaki S" first="Seigo" last="Terawaki">Seigo Terawaki</name>
<name sortKey="Terawaki, Seigo" sort="Terawaki, Seigo" uniqKey="Terawaki S" first="Seigo" last="Terawaki">Seigo Terawaki</name>
<name sortKey="Terawaki, Seigo" sort="Terawaki, Seigo" uniqKey="Terawaki S" first="Seigo" last="Terawaki">Seigo Terawaki</name>
<name sortKey="Wenger, Till" sort="Wenger, Till" uniqKey="Wenger T" first="Till" last="Wenger">Till Wenger</name>
<name sortKey="Wenger, Till" sort="Wenger, Till" uniqKey="Wenger T" first="Till" last="Wenger">Till Wenger</name>
<name sortKey="Wenger, Till" sort="Wenger, Till" uniqKey="Wenger T" first="Till" last="Wenger">Till Wenger</name>
</country>
</tree>
</affiliations>
</record>

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Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells

Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells

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