Author: Wang, Ran; Moniruzzaman, Md.; Shuffle, Eric; Lourie, Rohan; Hasnain, Sumaira Z
Title: Immune regulation of the unfolded protein response at the mucosal barrier in viral infection Document date: 2018_4_3
ID: 07dlf3zw_7
Snippet: Upon dissociation from GRP78, the transmembrane kinase PERK is activated by oligomerisation and autophosphorylation. PERK phosphorylates eukaryotic translation initiation factor 2a (eIF2a), which inhibits ribosome assembly leading to the inhibition of global protein translation, reducing ER load. Although protein translation is halted under ER stress conditions, translation of specific mRNAs is not subject to inhibition. For example, activating t.....
Document: Upon dissociation from GRP78, the transmembrane kinase PERK is activated by oligomerisation and autophosphorylation. PERK phosphorylates eukaryotic translation initiation factor 2a (eIF2a), which inhibits ribosome assembly leading to the inhibition of global protein translation, reducing ER load. Although protein translation is halted under ER stress conditions, translation of specific mRNAs is not subject to inhibition. For example, activating transcription factor 4 (ATF4) escapes translation inhibition, which ultimately leads to expression of genes that regulate amino acid metabolism and autophagy (discussed later). 5 Activated ATF4 in turn induces expression of GADD34, a phosphatase which regulates eIF2a phosphorylation. Once ER stress is resolved, eIF2a is dephosphorylated by GADD34protein phosphatase 1 complex to restore global protein synthesis.
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