PT  - JOURNAL ARTICLE
AU  - Andreia Mendes
AU  - Julien P Gigan
AU  - Christian Rodriguez Rodrigues
AU  - Sébastien A Choteau
AU  - Doriane Sanseau
AU  - Daniela Barros
AU  - Catarina Almeida
AU  - Voahirana Camosseto
AU  - Lionel Chasson
AU  - Adrienne W Paton
AU  - James C Paton
AU  - Rafael J Argüello
AU  - Ana-Maria Lennon-Duménil
AU  - Evelina Gatti
AU  - Philippe Pierre
TI  - Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4
AID  - 10.26508/lsa.202000865
DP  - 2021 Feb 01
TA  - Life Science Alliance
PG  - e202000865
VI  - 4
IP  - 2
4099  - https://www.life-science-alliance.org/content/4/2/e202000865.short
4100  - https://www.life-science-alliance.org/content/4/2/e202000865.full
SO  - Life Sci. Alliance2021 Feb 01; 4
AB  - 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.