title: Multiple inputs control sulfur-containing amino acid synthesis in Saccharomyces cerevisiae.
abstract: In Saccharomyces cerevisiae, transcription of the MET regulon, which encodes the proteins involved in the synthesis of the sulfur-containing amino acids methionine and cysteine, is repressed by the presence of either methionine or cysteine in the environment. This repression is accomplished by ubiquitination of the transcription factor Met4, which is carried out by the SCF(Met30) E3 ubiquitin ligase. Mutants defective in MET regulon repression reveal that loss of Cho2, which is required for the methylation of phosphatidylethanolamine to produce phosphatidylcholine, leads to induction of the MET regulon. This induction is due to reduced cysteine synthesis caused by the Cho2 defects, uncovering an important link between phospholipid synthesis and cysteine synthesis. Antimorphic mutants in S-adenosyl-methionine (SAM) synthetase genes also induce the MET regulon. This effect is due, at least in part, to SAM deficiency controlling the MET regulon independently of SAM's contribution to cysteine synthesis. Finally, the Met30 protein is found in two distinct forms whose relative abundance is controlled by the availability of sulfur-containing amino acids. This modification could be involved in the nutritional control of SCF(Met30) activity toward Met4.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Meru J
authors.initials: MJ
authors.lastname: Sadhu
authors.affiliation: Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moresco
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Anjali D
authors.initials: AD
authors.lastname: Zimmer
authors.affiliation: Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720 jrine@berkeley.edu.
authors.forename: Jasper
authors.initials: J
authors.lastname: Rine
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine / Q000096:biosynthesis*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics; D008715:Methionine / Q000096:biosynthesis*; D008716:Methionine Adenosyltransferase / Q000235:genetics; D008745:Methylation; D010713:Phosphatidylcholines / Q000096:biosynthesis; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000235:genetics; D010714:Phosphatidylethanolamines / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D044783:F-Box Proteins; C470285:MET30 protein, S cerevisiae; C073675:MET4 protein, S cerevisiae; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; C483858:phosphatidylethanolamine; D012436:S-Adenosylmethionine; D008715:Methionine; C494486:CHO2 protein, S cerevisiae; D050918:Phosphatidylethanolamine N-Methyltransferase; D043743:Ubiquitin-Protein Ligase Complexes; D008716:Methionine Adenosyltransferase; D003545:Cysteine