ArticleMolecular and cellular biology1991
Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein.
Article in Molecular and cellular biology, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79 citing papers in PubMed, 214 citations in OpenAlex.
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- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Robustness quantification of a mutant library screen revealed key genetic markers in yeast.Microbial cell factories · 2024Article
- Achieving the promise and avoiding the peril of chemical probes using genetics.Current opinion in structural biology · 2023Review
- The Rheb GTPase promotes pheromone blindness via a TORC1-independent pathway in the phytopathogenic fungus Ustilago maydis.PLoS genetics · 2022Article
- Purine Auxotrophic Starvation Evokes Phenotype Similar to Stationary Phase Cells in Budding Yeast.Journal of fungi (Basel, Switzerland) · 2021Article
- Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy.International journal of molecular sciences · 2021Review
- High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12.Biotechnology for biofuels · 2021Article
- Current Approaches and Future Directions for the Treatment of mTORopathies.Developmental neuroscience · 2021Review
- Host-induced gene silencing of BcTOR in Botrytis cinerea enhances plant resistance to grey mould.Molecular plant pathology · 2019Article
- mTOR as a central hub of nutrient signalling and cell growth.Nature cell biology · 2019Review
- Transcriptional and Epigenetic Regulation by the Mechanistic Target of Rapamycin Complex 1 Pathway.Journal of molecular biology · 2018Review
- Article
- mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders.International journal of molecular sciences · 2018Review
- Twenty-five years of mTOR: Uncovering the link from nutrients to growth.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Ubiquitin regulates TORC1 in yeast Saccharomyces cerevisiae.Molecular microbiology · 2016Article
- Tomato FK506 Binding Protein 12KD (FKBP12) Mediates the Interaction between Rapamycin and Target of Rapamycin (TOR).Frontiers in plant science · 2016Article
- Target of Rapamycin Is a Key Player for Auxin Signaling Transduction in Arabidopsis.Frontiers in plant science · 2016Article
- Protein profiling of mefloquine resistantInternational journal of mass spectrometry · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rapamycin is a macrolide antifungal agent with structural similarity to FK506. It exhibits potent immunosuppressive properties analogous to those of both FK506 and cyclosporin A (CsA). Unlike FK506 and CsA, however, rapamycin does not inhibit the transcription of early T-cell activation genes, including interleukin-2, but instead appears to block downstream events leading to T-cell activation. FK506 and CsA receptor proteins (FKBP and cyclophilin, respectively) have been identified and shown to be distinct members of a class of enzymes that possess peptidyl-prolyl cis-trans isomerase (PPIase) activity. Despite the apparent differences in their mode of action, rapamycin and FK506 act as reciprocal antagonists in vivo and compete for binding to FKBP. As a means of rapidly identifying a target protein for rapamycin in vivo, we selected and genetically characterized rapamycin-resistant mutants of Saccharomyces cerevisiae and isolated a yeast genomic fragment that confers drug sensitivity. We demonstrate that the resonse to rapamycin in yeast cells is mediated by a gene encoding a 114-amino-acid, approximately 13-kDa protein which has a high degree of sequence homology with human FKBP; we designated this gene RBP1 (for rapamycin-binding protein). The RBP1 protein (RBP) was expressed in Escherichia coli, purified to homogeneity, and shown to catalyze peptidyl-prolyl isomerization of a synthetic peptide substrate. PPIase activity was completely inhibited by rapamycin and FK506 but not by CsA, indicating that both macrolides bind to the recombinant protein. Expression of human FKBP in rapamycin-resistant mutants restored rapamycin sensitivity, indicating a functional equivalence between the yeast and human enzymes.
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