ArticleEukaryotic cell2004
FKBP12 controls aspartate pathway flux in Saccharomyces cerevisiae to prevent toxic intermediate accumulation.
Article in Eukaryotic cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Characterization and regulation of salt upregulated cyclophilin from a halotolerant strain of Penicillium oxalicum.Scientific reports · 2023Article
- FK506-binding protein, FKBP12, promotes serine utilization and negatively regulates threonine deaminase in fission yeast.iScience · 2022Article
- Molecular targets for antifungals in amino acid and protein biosynthetic pathways.Amino acids · 2021Review
- Physiological function of FKBP12, a primary target of rapamycin/FK506: a newly identified role in transcription of ribosomal protein genes in yeast.Current genetics · 2021Review
- Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae.PLoS genetics · 2020Article
- Potential targets for the development of new antifungal drugs.The Journal of antibiotics · 2018Review
- The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability.Nucleic acids research · 2018Article
- Article
- The contribution of bacterial genome engineering to sustainable development.Microbial biotechnology · 2017Article
- Optimality principles reveal a complex interplay of intermediate toxicity and kinetic efficiency in the regulation of prokaryotic metabolism.PLoS computational biology · 2017Article
- Inhibitors of amino acids biosynthesis as antifungal agents.Amino acids · 2015Review
- Accumulation of a threonine biosynthetic intermediate attenuates general amino acid control by accelerating degradation of Gcn4 via Pho85 and Cdk8.PLoS genetics · 2014Article
- The prolyl isomerase, FKBP25, interacts with RNA-engaged nucleolin and the pre-60S ribosomal subunit.RNA (New York, N.Y.) · 2014Article
- Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1Delta) mutants.Eukaryotic cell · 2010Article
- Fungal homoserine kinase (thr1Delta) mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation.Eukaryotic cell · 2010Article
- Cohesion group approach for evolutionary analysis of aspartokinase, an enzyme that feeds a branched network of many biochemical pathways.Microbiology and molecular biology reviews : MMBR · 2009Review
- Threonine biosynthetic genes are essential in Cryptococcus neoformans.Microbiology (Reading, England) · 2008Article
- Calcineurin regulation in fungi and beyond.Eukaryotic cell · 2008Review
- Identification of genes required for protection from doxorubicin by a genome-wide screen in Saccharomyces cerevisiae.Cancer research · 2007Article
- A novel lipoxygenase inhibitor Nordy attenuates malignant human glioma cell responses to chemotactic and growth stimulating factors.Journal of neuro-oncology · 2007Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
FKBP12 is a conserved member of the prolyl-isomerase enzyme family and serves as the intracellular receptor for FK506 that mediates immunosuppression in mammals and antimicrobial actions in fungi. To investigate the cellular functions of FKBP12 in Saccharomyces cerevisiae, we employed a high-throughput assay to identify mutations that are synthetically lethal with a mutation in the FPR1 gene, which encodes FKBP12. This screen identified a mutation in the HOM6 gene, which encodes homoserine dehydrogenase, the enzyme catalyzing the last step in conversion of aspartic acid into homoserine, the common precursor in threonine and methionine synthesis. Lethality of fpr1 hom6 double mutants was suppressed by null mutations in HOM3 or HOM2, encoding aspartokinase and aspartate beta-semialdehyde dehydrogenase, respectively, supporting the hypothesis that fpr1 hom6 double mutants are inviable because of toxic accumulation of aspartate beta-semialdehyde, the substrate of homoserine dehydrogenase. Our findings also indicate that mutation or inhibition of FKBP12 dysregulates the homoserine synthetic pathway by perturbing aspartokinase feedback inhibition by threonine. Because this pathway is conserved in fungi but not in mammals, our findings suggest a facile route to synergistic antifungal drug development via concomitant inhibition of FKBP12 and Hom6.
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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.