ArticleThe Journal of biological chemistry2013
Identification of C18:1-phytoceramide as the candidate lipid mediator for hydroxyurea resistance in yeast.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Enzymes of sphingolipid metabolism as transducers of metabolic inputs.Biochemical Society transactions · 2024Review
- Biological function, topology, and quantification of plasma membrane Ceramide.Advances in biological regulation · 2024Review
- Article
- The Many Faces of Lipids in Genome Stability (and How to Unmask Them).International journal of molecular sciences · 2021Review
- Yeast Sphingolipid Phospholipase GeneMolecular and cellular biology · 2020Article
- Visualizing bioactive ceramides.Chemistry and physics of lipids · 2018Review
- Sphingolipids and their metabolism in physiology and disease.Nature reviews. Molecular cell biology · 2018Review
- Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.Biochimica et biophysica acta · 2016Review
- The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation.Cell cycle (Georgetown, Tex.) · 2016Article
- Regulation of Sphingolipid Biosynthesis by the Morphogenesis Checkpoint Kinase Swe1.The Journal of biological chemistry · 2016Article
- Analysis of the Involvement of Different Ceramide Variants in the Response to Hydroxyurea Stress in Baker's Yeast.PloS one · 2016Article
- Ceramide signals for initiation of yeast mating-specific cell cycle arrest.Cell cycle (Georgetown, Tex.) · 2016Article
- Saccharomyces cerevisiae Is Dependent on Vesicular Traffic between the Golgi Apparatus and the Vacuole When Inositolphosphorylceramide Synthase Aur1 Is Inactivated.Eukaryotic cell · 2015Article
- Dynamics of the Heat Stress Response of Ceramides with Different Fatty-Acyl Chain Lengths in Baker's Yeast.PLoS computational biology · 2015Article
- Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell-cycle progression.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Role of Inositol Phosphosphingolipid Phospholipase C1, the Yeast Homolog of Neutral Sphingomyelinases in DNA Damage Response and Diseases.Journal of lipids · 2015Review
- Sphingolipids and mitochondrial function in budding yeast.Biochimica et biophysica acta · 2014Article
- The yeast sphingolipid signaling landscape.Chemistry and physics of lipids · 2014Review
- The protein kinase Sch9 is a key regulator of sphingolipid metabolism in Saccharomyces cerevisiae.Molecular biology of the cell · 2014Article
- Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses.Science signaling · 2013Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies showed that deletion of ISC1, the yeast homologue of the mammalian neutral sphingomyelinase, resulted in an increased sensitivity to hydroxyurea (HU). This raised an intriguing question as to whether sphingolipids are involved in pathways initiated by HU. In this study, we show that HU treatment led to a significant increase in Isc1 activity. Analysis of sphingolipid deletion mutants and pharmacological analysis pointed to a role for ceramide in mediating HU resistance. Lipid analysis revealed that HU induced increases in phytoceramides in WT cells but not in isc1Δ cells. To probe functions of specific ceramides, we developed an approach to supplement the medium with fatty acids. Oleate (C18:1) was the only fatty acid protecting isc1Δ cells from HU toxicity in a ceramide-dependent manner. Because phytoceramide activates protein phosphatases in yeast, we evaluated the role of CDC55, the regulatory subunit of ceramide-activated protein phosphatase PP2A. Overexpression of CDC55 overcame the sensitivity to HU in isc1Δ cells. However, addition of oleate did not protect the isc1Δ,cdc55Δ double mutant from HU toxicity. These results demonstrate that HU launches a lipid pathway mediated by a specific sphingolipid, C18:1-phytoceramide, produced by Isc1, which provides protection from HU by modulating Swe1 levels through the PP2A subunit Cdc55.
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Registered trials
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