Sadhu MJ, Moresco JJ, Zimmer AD, Yates JR, Rine J

In Saccharomyces cerevisiae, transcription of the MET regulon, encoding 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, carried out by ...

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the SCF(Met30) E3 ubiquitin ligase. Mutants defective in MET regulon repression revealed that loss of Cho2, required for the methylation of phosphatidylethanolamine to produce phosphatidylcholine, led to induction of the MET regulon. This induction was due to reduced cysteine synthesis caused by the Cho2 defects, uncovering an important link between phospholipid synthesis and cysteine synthesis. Antimorphic mutants in SAM synthetase genes also induced the MET regulon. This effect was due, at least in part, to SAM deficiency controlling the MET regulon independently of SAM's contribution to cysteine synthesis. Finally, the Met30 protein was found in two distinct forms whose relative abundance was controlled by the availability of sulfur-containing amino acids. This modification could be involved in the nutritional control of SCF(Met30) activity toward Met4.

Date: Mar. 19, 2014

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