Regulation of the Saccharomyces cerevisiae CKI1-encoded choline kinase by zinc depletion.
In the yeast Saccharomyces cerevisiae, the CKI1-encoded choline kinase catalyzes the committed step in the synthesis of phosphatidylcholine via the CDP-choline branch of the Kennedy pathway. Analysis of a P(CKI1)-lacZ reporter gene revealed that CKI1 expression was regulated by intracellular levels of the essential mineral zinc. Zinc depletion resulted in a concentration-dependent induction of CKI1 expression. This regulation was mediated by the zinc-sensing and zinc-inducible transcriptional activator Zap1p. A purified Zap1p probe interacted with two putative UAS(ZRE) sequences (ZRE1 and ZRE2) in the CKI1 promoter. Mutations of ZRE1 and ZRE2 to a nonconsensus UAS(ZRE) attenuated the induction of CKI1 expression in response to zinc depletion. A UAS(INO) element in the CKI1 promoter was responsible for stimulating CKI1 expression, but this element was not involved with the regulation by zinc depletion. The induction of CKI1 expression in zinc-depleted cells translated into increased choline kinase activity in vitro and in vivo, and an increase in phosphatidylcholine synthesis via the Kennedy pathway.
Soto
Aníbal
A
Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
Carman
George M
GM
D002797:Choline Kinase / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000235:genetics; D020218:Response Elements / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015032:Zinc / Q000172:deficiency / Q000494:pharmacology*
D010713:Phosphatidylcholines; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C103264:ZAP1 protein, S cerevisiae; D002797:Choline Kinase; D015032:Zinc