ArticleeLife2016
Ceapins inhibit ATF6α signaling by selectively preventing transport of ATF6α to the Golgi apparatus during ER stress.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 135 citations in OpenAlex.
- Chemical induction and reversal of photoreceptor dystrophy in retinal organoids.Stem cell reports · 2026Article
- Endoplasmic Reticulum Stress-Induced Endothelial Cell Pyroptosis Contributes to Pulmonary Vascular Remodeling and Pulmonary Arterial Hypertension via IRE1α/Caspase-3/GSDME Pathway.Journal of the American Heart Association · 2026Article
- PERK orchestrates an endoplasmic reticulum stress alternative splicing program via CLK1/SRSF1.Nature communications · 2026Article
- Synergistic Molecular Strategies for Targeting the Unfolded Protein Response in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Ceapin-A7 counteracts the protective effects of Lanreotide in endothelial cells.Aspects of molecular medicine · 2026Article
- Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review).Experimental and therapeutic medicine · 2026Review
- Chemical modulation of the unfolded protein response reveals an antiviral role for the PERK pathway in human coronavirus 229E infection.RSC chemical biology · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Chemo-/radiotherapy-induced cardiomyopathy: roles of mitochondria and endoplasmic reticulum.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Review
- FAM134B controls collagen I dynamics in hepatic stellate cell-driven fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Article
- Trimethylamine-N-oxide promotes fibrotic activation of quiescent valvular interstitial cells via endoplasmic reticulum stress.Scientific reports · 2025Article
- Targeting the unfolded protein response in cancer: exploiting endoplasmic reticulum stress for therapeutic intervention.Biochemical pharmacology · 2025Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- STK26 Promotes the Stabilization of ATF6 to Facilitate the Progression of Colorectal Cancer.International journal of molecular sciences · 2025Article
- TUDCA modulates drug bioavailability to regulate resistance to acute ER stress inMolecular biology of the cell · 2025Article
- ATF6 inhibition suppresses the protective effects of pasireotide in human and bovine endothelial cells.Vascular biology (Bristol, England) · 2025Article
- Pharmacologic Targeting of PDIA1 Inhibits NLRP3 Inflammasome Assembly and Activation.Israel journal of chemistry · 2024Article
- ATF6 Promotes Colorectal Cancer Growth and Stemness by Regulating the Wnt Pathway.Cancer research communications · 2024Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The membrane-bound transcription factor ATF6α is activated by proteolysis during endoplasmic reticulum (ER) stress. ATF6α target genes encode foldases, chaperones, and lipid biosynthesis enzymes that increase protein-folding capacity in response to demand. The off-state of ATF6α is maintained by its spatial separation in the ER from Golgi-resident proteases that activate it. ER stress induces trafficking of ATF6α. We discovered Ceapins, a class of pyrazole amides, as selective inhibitors of ATF6α signaling that do not inhibit the Golgi proteases or other UPR branches. We show that Ceapins block ATF6α signaling by trapping it in ER-resident foci that are excluded from ER exit sites. Removing the requirement for trafficking by pharmacological elimination of the spatial separation of the ER and Golgi apparatus restored cleavage of ATF6α in the presence of Ceapins. Washout of Ceapins resensitized ATF6α to ER stress. These results suggest that trafficking of ATF6α is regulated by its oligomeric state.
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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.