Co-regulation of yeast purine and phosphate pathways in response to adenylic nucleotide variations.
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.
Gauthier
Sébastien
S
Université Victor Segalen/Bordeaux 2, Institut de Biochimie et Génétique Cellulaires, Bordeaux, France.
Coulpier
Fanny
F
Jourdren
Laurent
L
Merle
Michel
M
Beck
Stefanie
S
Konrad
Manfred
M
Daignan-Fornier
Bertrand
B
Pinson
Benoît
B
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
D000227:Adenine Nucleotides; D005656:Fungal Proteins; D007527:Isoenzymes; D010710:Phosphates; D011687:Purines; D007288:Inosine; D000263:Adenylate Kinase; C110939:adenylate kinase 1; C030985:purine