| First Author | Mendes A | Year | 2021 |
| Journal | Life Sci Alliance | Volume | 4 |
| Issue | 2 | PubMed ID | 33443099 |
| Mgi Jnum | J:314593 | Mgi Id | MGI:6801939 |
| Doi | 10.26508/lsa.202000865 | Citation | Mendes A, et al. (2021) Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4. Life Sci Alliance 4(2) |
| abstractText | In stressed cells, phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) 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 eIF2alpha phosphorylation, mostly caused by the activation of the ER kinase PERK (EIF2AK3). Despite high p-eIF2alpha 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-beta 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 eIF2alpha phosphorylation is likely important to adapt DC homeostasis to the variations imposed by the immune contexts. |
