ArticleScientific reports2017
FTY720-induced endocytosis of yeast and human amino acid transporters is preceded by reduction of their inherent activity and TORC1 inhibition.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- A Limited Number of Amino Acid Permeases Are Crucial forInternational journal of microbiology · 2024Review
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- Art2 mediates selective endocytosis of methionine transporters during adaptation to sphingolipid depletion.Journal of cell science · 2023Article
- Expression of sphingosine-1-phosphate receptor 2 is correlated with migration and invasion of human colon cancer cells: A preliminary clinical study.Oncology letters · 2022Article
- CTP sensing and Mec1ATR-Rad53CHK1/CHK2 mediate a two-layered response to inhibition of glutamine metabolism.PLoS genetics · 2022Article
- Heterozygous Mutations in Aromatic Amino Acid Synthesis Genes Trigger TOR Pathway Activation inmicroPublication biology · 2022Article
- The key player in the pathogenesis of environmental influence of systemic lupus erythematosus: Aryl hydrocarbon receptor.Frontiers in immunology · 2022Review
- Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types-Tumour Microenvironment and Metabolism.International journal of molecular sciences · 2020Review
- Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae.PLoS genetics · 2020Article
- FTY720, a sphingosine analog, altered placentome histoarchitecture in ewes.Journal of animal science and biotechnology · 2020Article
- Ubiquitylation and endocytosis of the human LAT1/SLC7A5 amino acid transporter.Scientific reports · 2019Article
- Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs.Molecular & cellular proteomics : MCP · 2019Article
- In search of constrained FTY720 and phytosphingosine analogs as dual acting anticancer agents targeting metabolic and epigenetic pathways.European journal of medicinal chemistry · 2018Article
- Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.Journal of cell science · 2018Article
- Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets.International journal of molecular sciences · 2018Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FTY720 is a sphingoid base analog that acts as an anticancer agent in animal models. Its effect on tumor cells stems largely from its ability to trigger endocytosis of several nutrient transporters. The observation that FTY720 similarly stimulates downregulation of amino acid permeases in yeast suggests that the cellular mechanisms it targets, which are still poorly characterized, are evolutionarily conserved. We here report that adding FTY720 to yeast cells results in rapid inhibition of the intrinsic activity of multiple permeases. This effect is associated with inhibition of the TORC1 kinase complex, which in turn promotes ubiquitin-dependent permease endocytosis. Further analysis of the Gap1 permease showed that FTY720 elicits its ubiquitylation via the same factors that promote this modification when TORC1 is inhibited by rapamycin. We also show that FTY720 promotes endocytosis of the LAT1/SLC7A5 amino acid transporter in HeLa cells, this being preceded by loss of its transport activity and by mTORC1 inhibition. Our data suggest that in yeast, TORC1 deactivation resulting from FTY720-mediated inhibition of membrane transport elicits permease endocytosis. The same process seems to occur in human cells even though our data and previous reports suggest that FTY720 promotes transporter endocytosis via an additional mechanism insensitive to rapamycin.
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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.