Control of methionine biosynthesis genes by protein kinase CK2-mediated phosphorylation of Cdc34.
Methionine and metabolites such as S-adenosylmethionine (AdoMet) are of vital importance for eukaryotes; AdoMet is the main donor of methyl groups and is involved in expression control of the methionine biosynthesis genes (MET genes). Genome-wide expression profiling of protein kinase CK2 deletion strains of the budding yeast Saccharomyces cerevisiae has indicated a function for CK2 in MET gene control. Deletion of the regulatory CK2 subunits leads to MET gene repression, presumably due to an impaired phosphorylation of the ubiquitin-conjugating enzyme Cdc34, which controls the central MET gene transcription factor Met4. We show that CK2 phosphorylates Cdc34 at two sites and one of these, Ser282, has a significant impact on MET gene expression in vivo, and that high AdoMet levels inhibit CK2. The data provide evidence for a control of MET gene expression by protein kinase CK2-mediated phosphorylation of Cdc34, and appear to suggest a feedback control loop in which high AdoMet-levels are limiting CK2 activity and thus MET gene expression.
Barz
T
T
Biochemische Zellphysiologie (A135), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Ackermann
K
K
Pyerin
W
W
D064173:Anaphase-Promoting Complex-Cyclosome; D047390:Casein Kinase II / Q000494:pharmacology*; D015966:Gene Expression Regulation, Fungal; D008715:Methionine / Q000096:biosynthesis*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014170:Transformation, Genetic; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D029701:Saccharomyces cerevisiae Proteins; D008715:Methionine; C577449:CDC34 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D047390:Casein Kinase II