ArticleThe EMBO journal2020
Phosphorylation switches protein disulfide isomerase activity to maintain proteostasis and attenuate ER stress.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 99 citations in OpenAlex.
- Disulphide maintenance systems and proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- The protein disulfide isomerase P4HB/PDIA1 modulates cellular and misfolded forms of the prion protein.PLoS pathogens · 2026Article
- Review
- Transcription factor 19 modulates fatty acid elongation and unfolded protein response to attenuate palmitic acid-induced hepatic dysfunction.Nature communications · 2026Article
- Calcium-mediated calreticulin-IRE1α interaction drives dynamic fluctuation of IRE1α activity under chronic endoplasmic reticulum stress.Nature communications · 2026Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Integrative analysis identifies PIGK as an oncogenic glycosylphosphatidylinositol transamidase subunit with prognostic, immunological, and therapeutic relevance in head and neck cancer.International journal of medical sciences · 2026Article
- Mitochondria-associated membranes in heart failure: from molecular mechanisms to therapeutic targets.Frontiers in physiology · 2026Review
- Unfolded protein response in bronchopulmonary dysplasia: mechanisms, pathways, and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1.Hepatology (Baltimore, Md.) · 2026Article
- Article
- Comprehensive Analysis of the Putative Substratome of FAM20C, the Master Serine Kinase of the Secretory Pathway.Biomolecules · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- Article
- Myeloid-Derived LGALS9-P4HB Immune Interaction Promotes Metastasis in Gastric Cancer Through Enhanced Cell Proliferation and Lipid Metabolism.Journal of cellular and molecular medicine · 2025Article
- FAM20C: A key protein kinase in multiple diseases.Genes & diseases · 2025Review
- Review
- The genome and comparative transcriptome of the euryhaline model ciliate Paramecium duboscqui reveal adaptations to environmental salinity.BMC biology · 2024Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Accumulated unfolded proteins in the endoplasmic reticulum (ER) trigger the unfolded protein response (UPR) to increase ER protein folding capacity. ER proteostasis and UPR signaling need to be regulated in a precise and timely manner. Here, we identify phosphorylation of protein disulfide isomerase (PDI), one of the most abundant and critical folding catalysts in the ER, as an early event during ER stress. The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity. Importantly, PDI-S359A knock-in mice display enhanced IRE1α activation and liver damage under acute ER stress. We conclude that the Fam20C-PDI axis constitutes a post-translational response to maintain ER proteostasis and plays a vital role in protecting against ER stress-induced cell death.
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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.