Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4.

Autor:	Mendes A; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France.; Department of Medical Sciences, Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, University of Aveiro, Aveiro, Portugal.; International Associated Laboratory (LIA) CNRS 'Mistra', Marseille, France., Gigan JP; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France., Rodriguez Rodrigues C; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France., Choteau SA; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France.; Aix-Marseille Université, INSERM, Theories and Approaches of Genomic Complexity (TAGC), CENTURI, Marseille, France., Sanseau D; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France., Barros D; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France.; Department of Medical Sciences, Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, University of Aveiro, Aveiro, Portugal.; International Associated Laboratory (LIA) CNRS 'Mistra', Marseille, France., Almeida C; Department of Medical Sciences, Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, University of Aveiro, Aveiro, Portugal.; International Associated Laboratory (LIA) CNRS 'Mistra', Marseille, France., Camosseto V; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France.; International Associated Laboratory (LIA) CNRS 'Mistra', Marseille, France.; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France., Chasson L; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France., Paton AW; Department of Molecular and Biomedical Science, Research Centre for Infectious Diseases, University of Adelaide, Adelaide, Australia., Paton JC; Department of Molecular and Biomedical Science, Research Centre for Infectious Diseases, University of Adelaide, Adelaide, Australia., Argüello RJ; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France.; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France., Lennon-Duménil AM; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France., Gatti E; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France gatti@ciml.univ-mrs.fr.; Department of Medical Sciences, Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, University of Aveiro, Aveiro, Portugal.; International Associated Laboratory (LIA) CNRS 'Mistra', Marseille, France.; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France., Pierre P; Aix Marseille Université, Centre National de la Recherch Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille Luminy (CIML), CENTURI, Marseille, France pierre@ciml.univ-mrs.fr.; Department of Medical Sciences, Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, University of Aveiro, Aveiro, Portugal.; International Associated Laboratory (LIA) CNRS 'Mistra', Marseille, France.; INSERM U932, Institut Curie, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, Paris, France.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2020 Dec 21; Vol. 4 (2). Date of Electronic Publication: 2020 Dec 21 (Print Publication: 2021).
DOI:	10.26508/lsa.202000865
Abstrakt:	In stressed cells, phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation and gene expression known as the integrated stress response. We show here that DCs are characterized by high eIF2α phosphorylation, mostly caused by the activation of the ER kinase PERK (EIF2AK3). Despite high p-eIF2α levels, DCs display active protein synthesis and no signs of a chronic integrated stress response. This biochemical specificity prevents translation arrest and expression of the transcription factor ATF4 during ER-stress induction by the subtilase cytotoxin (SubAB). PERK inactivation, increases globally protein synthesis levels and regulates IFN-β expression, while impairing LPS-stimulated DC migration. Although the loss of PERK activity does not impact DC development, the cross talk existing between actin cytoskeleton dynamics; PERK and eIF2α phosphorylation is likely important to adapt DC homeostasis to the variations imposed by the immune contexts. (© 2020 Mendes et al.)
Databáze:	MEDLINE
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