ArticleBiochimica et biophysica acta2009
Ceramide synthase 1 is regulated by proteasomal mediated turnover.
Article in Biochimica et biophysica acta, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 54 citations in OpenAlex.
- Cannabidiol's cytotoxicity in pancreatic cancer is induced via an upregulation of ceramide synthase 1 and ER stress.Journal of cannabis research · 2024Article
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm.Frontiers in cell and developmental biology · 2024Review
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer.Scientific reports · 2019Article
- Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma.Oncotarget · 2017Article
- Sphingolipids and mitochondrial apoptosis.Journal of bioenergetics and biomembranes · 2016Review
- Enzyme Activities of the Ceramide Synthases CERS2-6 Are Regulated by Phosphorylation in the C-terminal Region.The Journal of biological chemistry · 2016Article
- Tumor Necrosis Factor-α (TNFα)-induced Ceramide Generation via Ceramide Synthases Regulates Loss of Focal Adhesion Kinase (FAK) and Programmed Cell Death.The Journal of biological chemistry · 2015Article
- Ceramide-induced apoptosis in renal tubular cells: a role of mitochondria and sphingosine-1-phoshate.International journal of molecular sciences · 2015Review
- Cell-type-specific expression pattern of ceramide synthase 2 protein in mouse tissues.Histochemistry and cell biology · 2013Article
- Regulation of de novo ceramide synthesis: the role of dihydroceramide desaturase and transcriptional factors NFATC and Hand2 in the hypoxic mouse heart.DNA and cell biology · 2013Article
- Pharmacogenetics of resistance to Cisplatin and other anticancer drugs and the role of sphingolipid metabolism.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Modulation of ceramide synthase activity via dimerization.The Journal of biological chemistry · 2012Article
- Ceramide synthases at the centre of sphingolipid metabolism and biology.The Biochemical journal · 2012Review
- Acyl chain specificity of ceramide synthases is determined within a region of 150 residues in the Tram-Lag-CLN8 (TLC) domain.The Journal of biological chemistry · 2012Article
- Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics.Chemical reviews · 2011Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Ceramide is an important bioactive lipid, intimately involved in many cellular functions, including the regulation of cell death, and in cancer and chemotherapy. Ceramide is synthesized de novo from sphinganine and acyl CoA via a family of 6 ceramide synthase enzymes, each having a unique preference for different fatty acyl CoA substrates and a unique tissue distribution. However, little is known regarding the regulation of these important enzymes. In this study we focus on ceramide synthase 1 (CerS1) which is the most structurally and functionally distinct of the enzymes, and describe a regulatory mechanism that specifically controls the level of CerS1 via ubiquitination and proteasome dependent protein turnover. We show that both endogenous and ectopically expressed CerS1 have rapid basal turnover and that diverse stresses including chemotherapeutic drugs, UV light and DTT can induce CerS1 turnover. The turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC). p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover. CerS1 is phosphorylated in vivo and activation of PKC increases the phosphorylation of the protein. This study reveals a novel and highly specific mechanism by which CerS1 protein levels are regulated and which directly impacts ceramide homeostasis.
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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.