ArticleeLife2020
The switch-like expression of heme-regulated kinase 1 mediates neuronal proteostasis following proteasome inhibition.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Stress granules at the crossroads of the proteostasis network.RNA biology · 2026Review
- Article
- Regulatory mechanism of heme-regulated inhibitor through autophosphorylation-driven activation and heme-induced deactivation.Journal of biochemistry · 2026Article
- Substrate Profiling of RNF216 Uncovers a Translation-Linked OTUD4 Regulatory Axis.bioRxiv : the preprint server for biology · 2026Article
- Proteasome-derived peptides: separating the trash from the recycling.Trends in biochemical sciences · 2025Review
- Cell type-specific in vivo proteomes with a multicopy mutant methionyl tRNA synthetase mouse line.Lab animal · 2025Article
- Regulation of translation elongation and integrated stress response in heat-shocked neurons.Cell reports · 2025Article
- HRI protein kinase in cytoplasmic heme sensing and mitochondrial stress response: Relevance to hematological and mitochondrial diseases.The Journal of biological chemistry · 2025Review
- Modulation of CREB3L2-ATF4 heterodimerization via proteasome inhibition and HRI activation in Alzheimer's disease pathology.Cell death & disease · 2025Article
- Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.Nature communications · 2024Article
- CaMKII suppresses proteotoxicity by phosphorylating BAG3 in response to proteasomal dysfunction.EMBO reports · 2024Article
- eIF2B localization and its regulation during the integrated stress response is cell-type specific.iScience · 2024Article
- Article
- Control of Selective mRNA Translation in Neuronal Subcellular Compartments in Health and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Involvement of Proteasomal and Endoplasmic Reticulum Stress in Neurodegeneration After Global Brain Ischemia.Molecular neurobiology · 2023Article
- Article
- A novel endoplasmic reticulum adaptation is critical for the long-lived Caenorhabditis elegans rpn-10 proteasomal mutant.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Stress Granules as Causes and Consequences of Translation Suppression.Antioxidants & redox signaling · 2023Review
- Depletion assisted hemin affinity (DAsHA) proteomics reveals an expanded landscape of heme-binding proteins in the human proteome.Metallomics : integrated biometal science · 2023Article
- PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response.Nature communications · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
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 endogenous heme levels are so low; HRI activity results in eIF2α phosphorylation and the resulting inhibition of translation. These data demonstrate a novel role for neuronal HRI that senses and responds to compromised function of the proteasome to restore proteostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.