Regulation of the Saccharomyces cerevisiae DPP1-encoded Diacylglycerol Pyrophosphate Phosphatase by Zinc

Han, Gil‐Soo; Johnston, Celeste N.; Chen, Xiaoming; Athenstaedt, Karin; Daum, Günther; Carman, George M.

doi:10.1074/jbc.m011421200

Cited by 66 publications

(85 citation statements)

References 66 publications

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“…This might be attributed to the relatively modest level of PIS1 induction (ϳ2-fold) compared with the Ͼ10-fold inductions of other Zap1p target genes (e.g. ZRT1, DPP1) (43,58). The differences between the magnitudes of induction of the PIS1 gene and other Zap1p target genes correlated with the relative binding efficiencies of GST-Zap1p 687-880 with the PIS1 promoter UAS ZRE 3 sequence compared with this sequence mutated to a consensus UAS ZRE sequence.…”

Section: Discussionmentioning

confidence: 99%

“…nutrient deprivation) by regulating the expression of enzyme activities including those involved in phospholipid synthesis (4,27,40,40,43,66,67). In particular, the stress condition of zinc depletion results in an increase in PI content which is attributed to elevated expression of PI synthase activity (40).…”

Section: Discussionmentioning

confidence: 99%

“…Saturated cultures were harvested, washed in deionized distilled water, diluted to 1 ϫ 10 6 cells/ml in medium containing 0 or 1.5 M zinc sulfate, and grown for 24 h. Cultures were then diluted to 1 ϫ 10 6 cells/ml and grown again in medium containing 0 or 1.5 M zinc sulfate. This growth routine with medium lacking zinc was used to deplete internal stores of zinc (43). Cells in liquid medium were grown to the exponential phase (1 ϫ 10 7 cells/ml), and cell numbers were determined spectrophotometrically at an absorbance of 600 nm.…”

Section: Methodsmentioning

confidence: 99%

“…Zap1p directly regulates UAS ZRE -containing genes (e.g. ZRT1, ZRT2, ZRT3, ZRC1, FET4, DPP1) whose expression is induced by zinc depletion (43,58,(62)(63)(64). Inspection of the PIS1 promoter revealed that it contains sequences that bear resemblance to the consensus UAS ZRE (see below).…”

Section: Effects Of the Zap1⌬ Mutation On The Regulation Of Pi Synthamentioning

confidence: 99%

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Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

Han

Iwanyshyn

et al. 2005

Journal of Biological Chemistry

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279, 21976 -21983).We examined the effects of zinc depletion on the regulation of the PIS1-encoded phosphatidylinositol synthase, the enzyme that catalyzes the formation of phosphatidylinositol from CDP-diacylglycerol and inositol. Phosphatidylinositol synthase activity increased when zinc was depleted from the growth medium. Analysis of a zrt1⌬ zrt2⌬ mutant defective in plasma membrane zinc transport indicated that the cytoplasmic levels of zinc were responsible for the regulation of phosphatidylinositol synthase. PIS1 mRNA, its encoded protein Pis1p, and the ␤-galactosidase activity driven by the P PIS1 -lacZ reporter gene were elevated in zinc-depleted cells. This indicated that the increase in phosphatidylinositol synthase activity was the result of a transcriptional mechanism. The zinc-mediated induction of the P PIS1 -lacZ reporter gene, Pis1p, and phosphatidylinositol synthase activity was lost in zap1⌬ mutant cells. These data indicated that the regulation of PIS1 gene expression by zinc depletion was mediated by the zinc-regulated transcription factor Zap1p. Direct interaction between glutathione S-transferase (GST)-Zap1p 687-880 and a putative upstream activating sequence (UAS) zinc-responsive element in the PIS1 promoter was demonstrated by electrophoretic mobility shift assays. Mutations in the UAS zinc-responsive element in the PIS1 promoter abolished the GSTZap1p 687-880 -DNA interaction in vitro and abolished the zinc-mediated regulation of the PIS1 gene in vivo. This work advances understanding of phospholipid synthesis regulation by zinc and the transcription control of the PIS1 gene. Phosphatidylinositol (PI)1 is the third most abundant phospholipid in the cellular membranes of the yeast Saccharomyces cerevisiae (1-3), and it is essential for the growth and metabolism of this model eukaryote (4 -6). In addition to being a major structural component of the membrane, PI serves as the precursor for sphingolipids (7,8), the D-3, D-4, and D-5 phosphoinositides (3, 9 -12), and glycosylphosphatidylinositol anchors (13, 14) (Fig. 1). Several of these PI-derived lipids and their metabolic products are prominent signaling molecules in S. cerevisiae and in higher eukaryotes that contribute to essential physiological functions (12,(15)(16)(17)(18)(19)(20).The enzyme responsible for the synthesis of PI in S. cerevisiae is the essential PIS1-encoded PI synthase (CDP-diacylglycerol:myo-inositol 3-phosphatidyltransferase, EC 2.7.8.11) (6, 21-23). This endoplasmic reticulum-associated (24) enzyme catalyzes the formation of PI and CMP from CDP-diacylglycerol and inositol (25) (Fig. 1). The regulation of PI synthase activity in vivo is largely governed by the availability of its substrates inositol and CDP-diacylglycerol (26 -28). Cellular inositol levels are controlled by expression of the INO1 gene encoding inositol-3-phosphate synthase and by inositol supplementation (26 -28). The levels of CDP-diacylglycerol are controlled through its utilization by the PI synthase enzyme itself and the competing activity of ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Effects Of the Zap1⌬ Mutation On The Regulation Of Pi Synthamentioning

confidence: 99%

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Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

Han

Iwanyshyn

et al. 2005

Journal of Biological Chemistry

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“…Strain YB1803 (MATa trp1 cho1⌬::LEU2) lacks the CHO1-encoded PS synthase (52). Standard methods were followed for the growth of S. cerevisiae (53,54). Cultures were grown at 30°C in YPD medium (1% yeast extract, 2% peptone, 2% glucose) or in complete synthetic medium (55) containing 2% glucose.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Phospholipid Synthesis in the Yeast cki1Δ eki1Δ Mutant Defective in the Kennedy Pathway

Choi

Sreenivas

Han

et al. 2004

Journal of Biological Chemistry

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In the yeast Saccharomyces cerevisiae, the most abundant phospholipid phosphatidylcholine is synthesized by the complementary CDP-diacylglycerol and Kennedy pathways. Using a cki1⌬ eki1⌬ mutant defective in choline kinase and ethanolamine kinase, we examined the consequences of a block in the Kennedy pathway on the regulation of phosphatidylcholine synthesis by the CDP-diacylglycerol pathway. The cki1⌬ eki1⌬ mutant exhibited increases in the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine via the CDP-diacylglycerol pathway. The increase in phospholipid synthesis correlated with increased activity levels of the CDPdiacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. However, other enzyme activities, including phosphatidylinositol synthase and phosphatidate phosphatase, were not affected in the cki1⌬ eki1⌬ mutant. For phosphatidylserine synthase, the enzyme catalyzing the committed step in the pathway, activity was regulated by increases in the levels of mRNA and protein. Decay analysis of CHO1 mRNA indicated that a dramatic increase in transcript stability was a major component responsible for the elevated level of phosphatidylserine synthase. These results revealed a novel mechanism that controls phospholipid synthesis in yeast.PC 1 is the most abundant phospholipid in the membranes of eukaryotic cells (1-4). It serves as a structural component of the membrane and as a source of bioactive lipids (e.g. lyso-PC, PA, DAG) (1-5). The importance of PC is underscored by the fact that alterations in its metabolism are linked to apoptosis (6 -9) and oncogenic transformation (10 -12). In the model eukaryote Saccharomyces cerevisiae, PC is synthesized by complementary pathways that are common to those found in mammalian cells 2 ( Fig. 1) (1,4,(13)(14)(15)(16)(17). In the CDP-DAG pathway, PC is synthesized from CDP-DAG via the reactions catalyzed by PS synthase (18 -20), PS decarboxylase (21-23), PE methyltransferase (24, 25), and phospholipid methyltransferase (24,26). In the CDP-choline branch of the Kennedy pathway, PC is synthesized from choline via the reactions catalyzed by choline kinase (27), phosphocholine cytidylyltransferase (28), and choline phosphotransferase (29,30). Analyses of mutations in S. cerevisiae (4, 31, 32), as well as in mammalian cells (33,34) indicate that the physiological role(s) of PC synthesized by the two pathways are different.The contribution of the CDP-DAG and Kennedy pathways for PC synthesis in wild type S. cerevisiae is dependent on the exogenous supply of choline (35). When grown in the presence of choline, yeast primarily synthesizes PC via the Kennedy pathway (35). On the other hand, when cells are grown in the absence of choline, PC is primarily synthesized via the CDP-DAG pathway (35). Yet, even under this growth condition, the Kennedy pathway still contributes to the synthesis of PC (36 -41). The choline required for the Kenne...

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2001

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (5 weeks journals ‐ search completed 13th June 2001)

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Regulation of the Saccharomyces cerevisiae DPP1-encoded Diacylglycerol Pyrophosphate Phosphatase by Zinc

Cited by 66 publications

References 66 publications

Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

Regulation of the PIS1-encoded Phosphatidylinositol Synthase in Saccharomyces cerevisiae by Zinc

Regulation of Phospholipid Synthesis in the Yeast cki1Δ eki1Δ Mutant Defective in the Kennedy Pathway

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