ArticleeLife2016
Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
156 citing papers in PubMed, 245 citations in OpenAlex.
- Coordinated control of proteasome subunit gene expression promotes stress resistance, proteostasis, and longevity.GeroScience · 2026Article
- Unveiling Novel Molecular Candidate Targets of Loratadine, Raloxifene, and Sorafenib in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- The Nematicide Tioxazafen Disrupts Proteasome Function via Cytochrome P450 Bioactivation.bioRxiv : the preprint server for biology · 2026Article
- Interplay between proteostasis pathways and innate immune responses inInfection and immunity · 2026Review
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.Cell death & disease · 2026Article
- The ubiquitin-proteasome pathway mediates selective degradation of unloaded Argonaute proteins in C. elegans.Genetics · 2026Article
- Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions.Aging cell · 2026Article
- NFE2L1/Nrf1 forms a coactivator complex post-peptide:Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Circadian-shaped immune variability predicts infection outcome.Science advances · 2026Article
- Intersections between proteostasis and immunity: insights from Caenorhabditis elegans.Disease models & mechanisms · 2026Review
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.bioRxiv : the preprint server for biology · 2025Article
- Cohesin forms fountains at active enhancers in C. elegans.Nature communications · 2025Article
- Anthracyclines attenuate Nrf1-dependent proteolytic pathways and potentiate proteasome inhibitor cytotoxicity.Molecular biology of the cell · 2025Article
- Natural SEL1L variants rescue a model of NGLY1 deficiency and modify ERAD function and proteasome sensitivity.PLoS genetics · 2025Article
- NGLY1 deficiency - clinical features and therapeutic strategy.Journal of human genetics · 2025Review
- Article
- Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.PLoS genetics · 2025Article
- SQST-1/p62-regulated SKN-1/Nrf mediates a phagocytic stress response via transcriptional activation of lyst-1/LYST.PLoS genetics · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
96 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Proteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular function, transcription of proteasome subunit genes is induced in response to proteasome dysfunction caused by pathogen attacks or proteasome inhibitor drugs. In Caenorhabditis elegans, this response requires SKN-1, a transcription factor related to mammalian Nrf1/2. Here, we use comprehensive genetic analyses to identify the pathway required for C. elegans to detect proteasome dysfunction and activate SKN-1. Genes required for SKN-1 activation encode regulators of ER traffic, a peptide N-glycanase, and DDI-1, a conserved aspartic protease. DDI-1 expression is induced by proteasome dysfunction, and we show that DDI-1 is required to cleave and activate an ER-associated isoform of SKN-1. Mammalian Nrf1 is also ER-associated and subject to proteolytic cleavage, suggesting a conserved mechanism of proteasome surveillance. Targeting mammalian DDI1 protease could mitigate effects of proteasome dysfunction in aging and protein aggregation disorders, or increase effectiveness of proteasome inhibitor cancer chemotherapies.
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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.