ArticleThe Journal of biological chemistry2015
Expression of the ORMDLS, modulators of serine palmitoyltransferase, is regulated by sphingolipids in mammalian cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Characterization of novel and recurrentJournal of neuromuscular diseases · 2026Article
- ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Altered sphingolipid biosynthetic flux and lipoprotein trafficking contribute to trans-fat-induced atherosclerosis.Cell metabolism · 2025Article
- ORMDL in metabolic health and disease.Pharmacology & therapeutics · 2023Review
- SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Article
- Neuronal Ganglioside and Glycosphingolipid (GSL) Metabolism and Disease : Cascades of Secondary Metabolic Errors Can Generate Complex Pathologies (in LSDs).Advances in neurobiology · 2023Article
- Sphingolipids in neurodegenerative diseases.Frontiers in neuroscience · 2023Review
- Targeting the Sphingolipid Rheostat in Gliomas.International journal of molecular sciences · 2022Review
- Sphingolipids and Asthma.Advances in experimental medicine and biology · 2022Article
- Sphingolipid Metabolism and Signaling in Endothelial Cell Functions.Advances in experimental medicine and biology · 2022Review
- Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis.Nature medicine · 2021Article
- Characteristics and Mechanisms of a Sphingolipid-associated Childhood Asthma Endotype.American journal of respiratory and critical care medicine · 2021Article
- Structural insights into the regulation of human serine palmitoyltransferase complexes.Nature structural & molecular biology · 2021Article
- Dissecting the regulatory roles of ORM proteins in the sphingolipid pathway of plants.PLoS computational biology · 2021Article
- Unregulated Sphingolipid Biosynthesis in Gene-Edited ArabidopsisThe Plant cell · 2020Article
- A genome-wide CRISPR/Cas9 screen reveals that the aryl hydrocarbon receptor stimulates sphingolipid levels.The Journal of biological chemistry · 2020Article
- Expression Patterns and Prognostic Values of ORMDL1 in Different Cancers.BioMed research international · 2020Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The relationship between serine palmitoyltransferase (SPT) activity and ORMDL regulation of sphingolipid biosynthesis was investigated in mammalian HEK293 cells. Each of the three human ORMDLs reduced the increase in long-chain base synthesis seen after overexpression of wild-type SPT or SPT containing the C133W mutation in hLCB1, which produces the non-catabolizable sphingoid base, 1-deoxySa. ORMDL-dependent repression of sphingoid base synthesis occurred whether SPT was expressed as individual subunits or as a heterotrimeric single-chain SPT fusion protein. Overexpression of the single-chain SPT fusion protein under the control of a tetracycline-inducible promoter in stably transfected cells resulted in increased endogenous ORMDL expression. This increase was not transcriptional; there was no significant increase in any of the ORMDL mRNAs. Increased ORMDL protein expression required SPT activity since overexpression of a catalytically inactive SPT with a mutation in hLCB2a had little effect. Significantly, increased ORMDL expression was also blocked by myriocin inhibition of SPT as well as fumonisin inhibition of the ceramide synthases, suggesting that increased expression is a response to a metabolic signal. Moreover, blocking ORMDL induction with fumonisin treatment resulted in significantly greater increases in in vivo SPT activity than was seen when ORMDLs were allowed to increase, demonstrating the physiological significance of this response.
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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.