ArticleMolecular and cellular biology1993
The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae.
Article in Molecular and cellular biology, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 85 citations in OpenAlex.
- V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.Biomolecules · 2025Review
- The Virulence Factor Macrophage Infectivity Potentiator (Mip) Influences Branched-Chain Amino Acid Metabolism and Pathogenicity ofMetabolites · 2023Article
- Article
- Interactions of FK506 and Rapamycin With FK506 Binding Protein 12 in Opportunistic Human Fungal Pathogens.Frontiers in molecular biosciences · 2020Review
- A novel ER membrane protein Ehg1/May24 plays a critical role in maintaining multiple nutrient permeases in yeast under high-pressure perturbation.Scientific reports · 2019Article
- Tryptophan confers resistance to SDS-associated cell membrane stress in Saccharomyces cerevisiae.PloS one · 2019Article
- Acetaminophen reduces the protein levels of high affinity amino acid permeases and causes tryptophan depletion.Amino acids · 2018Article
- Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import.PLoS genetics · 2014Article
- Identification of the novel interacting partners of the mammalian target of rapamycin complex 1 in human CCRF-CEM and HEK293 cells.International journal of molecular sciences · 2014Article
- Pressure-induced endocytic degradation of the Saccharomyces cerevisiae low-affinity tryptophan permease Tat1 is mediated by Rsp5 ubiquitin ligase and functionally redundant PPxY motif proteins.Eukaryotic cell · 2013Article
- Functional profiling discovers the dieldrin organochlorinated pesticide affects leucine availability in yeast.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Phospholipid flippases Lem3p-Dnf1p and Lem3p-Dnf2p are involved in the sorting of the tryptophan permease Tat2p in yeast.The Journal of biological chemistry · 2013Article
- Article
- Inference of protein complex activities from chemical-genetic profile and its applications: predicting drug-target pathways.PLoS computational biology · 2008Article
- Article
- Regulation of salt tolerance by Torulaspora delbrueckii calcineurin target Crz1p.Eukaryotic cell · 2006Article
- Activity of the yeast Tat2p tryptophan permease is sensitive to the anti-tumor agent 4-phenylbutyrate.Current genetics · 2004Article
- Quantitative genome-wide analysis of yeast deletion strain sensitivities to oxidative and chemical stress.Comparative and functional genomics · 2004Article
- Pressure-induced differential regulation of the two tryptophan permeases Tat1 and Tat2 by ubiquitin ligase Rsp5 and its binding proteins, Bul1 and Bul2.Molecular and cellular biology · 2003Article
- Volatile anesthetics affect nutrient availability in yeast.Genetics · 2002Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of peptidyl-prolyl cis-trans isomerases. Cyclosporin A binds cyclophilins, whereas FK506 and rapamycin bind FK506-binding proteins (FKBPs). Cyclophilins and FKBPs are ubiquitous, abundant, and targeted to multiple cellular compartments, and they may fold proteins in vivo. Previously, a 12-kDa cytoplasmic FKBP was shown to be only one of at least two FK506-sensitive targets in the yeast Saccharomyces cerevisiae. We find that a second FK506-sensitive target is required for amino acid import. Amino acid-auxotrophic yeast strains (trp1 his4 leu2) are FK506 sensitive, whereas prototrophic strains (TRP1 his4 leu2, trp1 HIS4 leu2, and trp1 his4 LEU2) are FK506 resistant. Amino acids added exogenously to the growth medium mitigate FK506 toxicity. FK506 induces GCN4 expression, which is normally induced by amino acid starvation. FK506 inhibits transport of tryptophan, histidine, and leucine into yeast cells. Lastly, several genes encoding proteins involved in amino acid import or biosynthesis confer FK506 resistance. These findings demonstrate that FK506 inhibits amino acid import in yeast cells, most likely by inhibiting amino acid transporters. Amino acid transporters are integral membrane proteins which import extracellular amino acids and constitute a protein family sharing 30 to 35% identity, including eight invariant prolines. Thus, the second FK506-sensitive target in yeast cells may be a proline isomerase that plays a role in folding amino acid transporters during transit through the secretory pathway.
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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.