ArticleMolecular and cellular biology2001
Yeast AMP pathway genes respond to adenine through regulated synthesis of a metabolic intermediate.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 95 citations in OpenAlex.
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- Phylogenetic debugging of a complete human biosynthetic pathway transplanted into yeast.Nucleic acids research · 2020Article
- Selection markers for transformation of the sequenced reference monokaryon Okayama 7/#130 and homokaryon AmutBmut ofFungal biology and biotechnology · 2020Article
- A quantitative screen for metabolic enzyme structures reveals patterns of assembly across the yeast metabolic network.Molecular biology of the cell · 2019Article
- Purine Homeostasis Is Necessary for Developmental Timing, Germline Maintenance and Muscle Integrity inGenetics · 2019Article
- Dual control of NADeLife · 2019Article
- Metabolomics and proteomics identify the toxic form and the associated cellular binding targets of the anti-proliferative drug AICAR.The Journal of biological chemistry · 2019Article
- Yeast to Study Human Purine Metabolism Diseases.Cells · 2019Review
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- Uncovering global metabolic response to cordycepin production in Cordyceps militaris through transcriptome and genome-scale network-driven analysis.Scientific reports · 2018Article
- Gene dosage effects in yeast support broader roles for the LOG1, HAM1 and DUT1 genes in detoxification of nucleotide analogues.PloS one · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Saccharomyces cerevisiae, AMP biosynthesis genes (ADE genes) are transcriptionally activated in the absence of extracellular purines by the Bas1p and Bas2p (Pho2p) transcription factors. We now show that expression of the ADE genes is low in mutant strains affected in the first seven steps of the pathway, while it is constitutively derepressed in mutant strains affected in later steps. Combined with epistasy studies, these results show that 5'-phosphoribosyl-4-succinocarboxamide-5-aminoimidazole (SAICAR), an intermediate metabolite of the pathway, is needed for optimal activation of the ADE genes. Two-hybrid studies establish that SAICAR is required to promote interaction between Bas1p and Bas2p in vivo, while in vitro experiments suggest that the effect of SAICAR on Bas1p-Bas2p interaction could be indirect. Importantly, feedback inhibition by ATP of Ade4p, catalyzing the first step of the pathway, appears to regulate SAICAR synthesis in response to adenine availability. Consistently, both ADE4 dominant mutations and overexpression of wild-type ADE4 lead to deregulation of ADE gene expression. We conclude that efficient transcription of yeast AMP biosynthesis genes requires interaction between Bas1p and Bas2p which is promoted in the presence of a metabolic intermediate whose synthesis is controlled by feedback inhibition of Ade4p acting as the purine nucleotide sensor within the cell.
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