ArticleDevelopmental cell2018
The UPR Activator ATF6 Responds to Proteotoxic and Lipotoxic Stress by Distinct Mechanisms.
Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- The interaction between endoplasmic reticulum stress and ferroptosis in ovarian diseases.Journal of ovarian research · 2026Pooled it
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- mTOR signaling contributes to system-driven rhythmic gene expression in mouse liver.Science advances · 2026Article
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- A novel 14-deoxy-12-hydroxyandrographolide analogue promotes apoptosis in colorectal cancer through ROS-dependent endoplasmic reticulum stress activation.Discover oncology · 2026Article
- Overnutrition in mice impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite remarkable thyroidal adaptations.The Journal of clinical investigation · 2026Article
- Inhibition of N-Terminal Acetyltransferase C Mitigates Endoplasmic Reticulum Stress-Mediated Muscle Atrophy in Cancer Cachexia.Journal of cachexia, sarcopenia and muscle · 2026Article
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The active secretion of a subunit of IL-12 by tissue cells is regulated by Valosin-Containing Protein and intracellular calcium redistribution.bioRxiv : the preprint server for biology · 2026Article
- Dysregulation of the AMPK-SREBP1-FASN axis in MASLD: driving a vicious cycle of lipotoxicity and metabolic-immune crosstalk.Lipids in health and disease · 2026Review
- Protein quality control and antigen presentation in the development of hepatitis B-related hepatocellular carcinoma.Frontiers in pharmacology · 2026Review
- A proteomic signature of vascular dysfunction linked to tauopathy and degeneration in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- Growth hormone - releasing hormone in the immune system.Reviews in endocrine & metabolic disorders · 2025Review
- PERK-dependent reciprocal crosstalk between ER and non-centrosomal microtubules coordinates ER architecture and cell shape.Cell reports · 2025Article
- Reprograming gene expression in 'hibernating'eLife · 2025Article
- Early-life antibiotic exposure aggravates hepatic steatosis through enhanced endotoxemia and lipotoxic effects driven by gutMedComm · 2025Article
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Gene module reconstruction identifies cellular differentiation processes and the regulatory logic of specialized secretion in zebrafish.Developmental cell · 2025Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The unfolded protein response (UPR) is induced by proteotoxic stress of the endoplasmic reticulum (ER). Here we report that ATF6, a major mammalian UPR sensor, is also activated by specific sphingolipids, dihydrosphingosine (DHS) and dihydroceramide (DHC). Single mutations in a previously undefined transmembrane domain motif that we identify in ATF6 incapacitate DHS/DHC activation while still allowing proteotoxic stress activation via the luminal domain. ATF6 thus possesses two activation mechanisms: DHS/DHC activation and proteotoxic stress activation. Reporters constructed to monitor each mechanism show that phenobarbital-induced ER membrane expansion depends on transmembrane domain-induced ATF6. DHS/DHC addition preferentially induces transcription of ATF6 target lipid biosynthetic and metabolic genes over target ER chaperone genes. Importantly, ATF6 containing a luminal achromatopsia eye disease mutation, unresponsive to proteotoxic stress, can be activated by fenretinide, a drug that upregulates DHC, suggesting a potential therapy for this and other ATF6-related diseases including heart disease and stroke.
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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.