Lys80p of Saccharomyces cerevisiae, previously proposed as a specific repressor of LYS genes, is a pleiotropic regulatory factor identical to Mks1p.
In Saccharomyces cerevisiae, an intermediate of the lysine pathway, alpha-aminoadipate semialdehyde (alpha AASA), acts as a coinducer for the transcriptional activation of LYS genes by Lys14p. The limitation of the production of this intermediate through feedback inhibition of the first step of the pathway results in apparent repression by lysine. Previously, the lys80 mutations, reducing the lysine repression and increasing the production of lysine, were interpreted as impairing a repressor of LYS genes expression. In order to understand the role of Lys80p in the control of the lysine pathway, we have analysed the effects of mutations epistatic to lys80 mutations. The effects of lys80 mutations on LYS genes expression were dependent on the integrity of the activation system (Lys14p and alpha AASA). The increased production of lysine in lys80 mutants appeared to result from an improvement of the metabolic flux through the pathway and was correlated to an increase of the alpha-ketoglutarate pool and of the level of several enzymes of the tricarboxylic acid cycle. The LYS80 genes has been cloned and sequenced; it turned out to be identical to gene MKS1 cloned as a gene encoding a negative regulator of the RAS-cAMP pathway. We conclude that Lys80p is a pleiotropic regulatory factor rather than a specific repressor of LYS genes.
Feller
A
A
Laboratoire de Microbiologie, Faculté des Sciences, Université Libre de Bruxelles, Belgium.
Ramos
F
F
Piérard
A
A
Dubois
E
E
D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002952:Citric Acid Cycle / Q000235:genetics; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016153:Genes, Suppressor; D007656:Ketoglutaric Acids / Q000378:metabolism; D008239:Lysine / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
D005656:Fungal Proteins; D007656:Ketoglutaric Acids; C080921:MKS1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D015074:2-Aminoadipic Acid; C000061:allysine; D008239:Lysine