title: Co-regulation of yeast purine and phosphate pathways in response to adenylic nucleotide variations.
abstract: Adenylate kinase (Adk1p) is a pivotal enzyme in both energetic and adenylic nucleotide metabolisms. In this paper, using a transcriptomic analysis, we show that the lack of Adk1p strongly induced expression of the PHO and ADE genes involved in phosphate utilization and AMP de novo biosynthesis respectively. Isolation and characterization of adk1 point mutants affecting PHO5 expression revealed that all these mutations also severely affected Adk1p catalytic activity, as well as PHO84 and ADE1 transcription. Furthermore, overexpression of distantly related enzymes such as human adenylate kinase or yeast UMP kinase was sufficient to restore regulation. These results demonstrate that adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways. We also establish that adk1 deletion and purine limitation have similar effects on both adenylic nucleotide pool and PHO84 or ADE17 expression. Finally, we show that, in the adk1 mutant, upregulation of ADE1 depends on synthesis of the previously described effector(s) (S)AICAR ((N-succinyl)-5-aminoimidazol-4-carboxamide ribotide), while upregulation of PHO84 necessitates the Spl2p positive regulator. This work reveals that adenylic nucleotide availability is a key signal used by yeast to co-ordinate phosphate utilization and purine synthesis.
authors.affiliation: Université Victor Segalen/Bordeaux 2, Institut de Biochimie et Génétique Cellulaires, Bordeaux, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gauthier
authors.forename: Fanny
authors.initials: F
authors.lastname: Coulpier
authors.forename: Laurent
authors.initials: L
authors.lastname: Jourdren
authors.forename: Michel
authors.initials: M
authors.lastname: Merle
authors.forename: Stefanie
authors.initials: S
authors.lastname: Beck
authors.forename: Manfred
authors.initials: M
authors.lastname: Konrad
authors.forename: Bertrand
authors.initials: B
authors.lastname: Daignan-Fornier
authors.forename: Benoît
authors.initials: B
authors.lastname: Pinson
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D007288:Inosine / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D010710:Phosphates / Q000378:metabolism*; D017354:Point Mutation; D011687:Purines / Q000378:metabolism*; D017384:Sequence Deletion; D015003:Yeasts / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D005656:Fungal Proteins; D007527:Isoenzymes; D010710:Phosphates; D011687:Purines; D007288:Inosine; D000263:Adenylate Kinase; C110939:adenylate kinase 1; C030985:purine