The switch-like expression of heme-regulated kinase 1 mediates neuronal proteostasis following proteasome inhibition.

ABSTRACT: We examined the feedback between the major protein degradation pathway, the ubiquitin-proteasome system (UPS), and protein synthesis in rat and mouse neurons. When protein degradation was inhibited, we observed a coordinate dramatic reduction in nascent protein synthesis in neuronal cell bodies and dendrites. The mechanism for translation inhibition involved the phosphorylation of eIF2α, surprisingly mediated by eIF2α kinase 1, or heme-regulated kinase inhibitor (HRI). Under basal conditions, neuronal expression of HRI is barely detectable. Following proteasome inhibition, HRI protein levels increase owing to stabilization of HRI and enhanced translation, likely via the increased availability of tRNAs for its rare codons. Once expressed, HRI is constitutively active in neurons because endo

SUBMITTER: Alvarez-Castelao B 

PROVIDER: S-EPMC7224698 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature