ArticleCell death & disease2017
PDI is an essential redox-sensitive activator of PERK during the unfolded protein response (UPR).
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 119 citations in OpenAlex.
- P1D6 inhibits FnBP-induced extracellular proteome remodeling: proteomic evidence for a novel intervention strategy in atopic dermatitis.Molecular medicine (Cambridge, Mass.) · 2026Article
- UPR-CEBPB-MIF Signaling Links to Macrophage Polarization and an Immunosuppressive Tumor Microenvironment in Clear Cell Renal Cell Carcinoma.Annals of surgical oncology · 2026Article
- The Integrated Stress Response Protein, eIF2α, Modulates UPRCardiovascular toxicology · 2026Article
- SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis.Nature cell biology · 2026Article
- S-nitrosylation contributes to ER stress and aggresome formation in secosterol-B-mediated endothelial dysfunction.Journal of lipid research · 2026Article
- SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis.bioRxiv : the preprint server for biology · 2026Article
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- A Small-Molecule Activator of Sarco/Endoplasmic Reticulum CaACS pharmacology & translational science · 2025Article
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- USP5-induced deubiquitination of P4HB alleviates ER stress-mediated apoptosis in intestinal ischemia/reperfusion.Cellular and molecular life sciences : CMLS · 2025Article
- The role of redox signaling in mitochondria and endoplasmic reticulum regulation in kidney diseases.Archives of toxicology · 2025Review
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- Potential drug targets for ovarian cancer identified through Mendelian randomization and colocalization analysis.Journal of ovarian research · 2025Article
- Renal Ischemia Induces Endoplasmic Reticulum Stress and Impairs the Reparative Potency of Scattered Tubular-Like Cells.American journal of nephrology · 2025Article
- Sulindac exhibits anti-proliferative and anti-invasive effects and enhances the sensitivity to paclitaxel in ovarian cancer.Frontiers in pharmacology · 2025Article
- P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker.Oncogenesis · 2024Article
- Review
- Analysis of Punicalin and Punicalagin Interaction with PDIA3 and PDIA1.International journal of molecular sciences · 2024Article
- The role of endoplasmic reticulum stress in the pathogenesis of oral diseases.Journal of the Korean Association of Oral and Maxillofacial Surgeons · 2024Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) that results in transient suppression of protein translation to allow recovery but leads to cell death when stress cannot be resolved. Central to initiation of the UPR is the activation of the ER transmembrane kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). Here we report that the thiol oxidoreductase ERp57 and protein disulfide isomerase-A1 (PDI), which belong to the same family of luminal ER oxidoreductases, have strikingly opposing roles in the regulation of PERK function. In HCT116 colon carcinoma cells, lentiviral depletion of ERp57 resulted in oxidation of PDI and activation of PERK, whereas depletion or chemical inhibition of PDI reduced PERK signaling and sensitized the cancer cells to hypoxia and ER stress. We conclude that oxidized PDI acts as a PERK activator, whereas ERp57 keeps PDI in a reduced state in the absence of ER stress. Thus, our study defines a new interface between metabolic redox signaling and PERK-dependent activation of the UPR and has the potential to influence future cancer therapies that target PERK signaling.
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