Regulation of Phospholipid Biosynthetic Enzymes by the Level of CDP-Diacylglycerol Synthase Activity

Shen, Haifa; Dowhan, William

doi:10.1074/jbc.272.17.11215

Cited by 41 publications

(34 citation statements)

References 43 publications

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“…Each bar is the mean of at least three independent transformants. (Summers et al 1988;McGraw and Henry 1989;White et al 1991;Shen and Dowhan 1997;Ouyang et al 1999;Elkhaimi et al 2000). However, the mechanism for inositol excretion remains unknown; thus it was reasonable to predict that some mutants from the VYDS screen might affect inositol excretion but not repression of INO1 expression.…”

Section: A Genomewide Screen Identified 89 Opimentioning

confidence: 99%

“…However, the ability of PC branch precursors (E, MME, DME, and C) to suppress the Opi À phenotype can also be observed in repressing conditions. For example, blocks in de novo PC biosynthesis are defective in inositol-mediated repression of the INO1 gene and its protein product; however, this defect is suppressed by addition of PC branch precursors (Letts and Henry 1985;Summers et al 1988;McGraw and Henry 1989;Shen and Dowhan 1997). To determine if this property applied to any of the new Opi À mutants, we chose two mutants that affect PC biosynthesis (fun26 and yol032w) and tested them for defects in INO1-lacZ regulation (Figure 7).…”

Section: A Genomewide Screen Identified 89 Opimentioning

confidence: 99%

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Genomic Analysis of the Opi− Phenotype

2006

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Most of the phospholipid biosynthetic genes of Saccharomyces cerevisiae are coordinately regulated in response to inositol and choline. Inositol affects the intracellular levels of phosphatidic acid (PA). Opi1p is a repressor of the phospholipid biosynthetic genes and specifically binds PA in the endoplasmic reticulum. In the presence of inositol, PA levels decrease, releasing Opi1p into the nucleus where it represses transcription. The opi1 mutant overproduces and excretes inositol into the growth medium in the absence of inositol and choline (Opi À phenotype). To better understand the mechanism of Opi1p repression, the viable yeast deletion set was screened to identify Opi À mutants. In total, 89 Opi À mutants were identified, of which 7 were previously known to have the Opi À phenotype. The Opi À mutant collection included genes with roles in phospholipid biosynthesis, transcription, protein processing/synthesis, and protein trafficking. Included in this set were all nonessential components of the NuA4 HAT complex and six proteins in the Rpd3p-Sin3p HDAC complex. It has previously been shown that defects in phosphatidylcholine synthesis (cho2 and opi3) yield the Opi À phenotype because of a buildup of PA. However, in this case the Opi À phenotype is conditional because PA can be shuttled through a salvage pathway (Kennedy pathway) by adding choline to the growth medium. Seven new mutants present in the Opi À collection ( fun26, kex1, nup84, tps1, mrpl38, mrpl49, and opi10/yol032w) were also suppressed by choline, suggesting that these affect PC synthesis. Regulation in response to inositol is also coordinated with the unfolded protein response (UPR). Consistent with this, several Opi À mutants were found to affect the UPR (yhi9, ede1, and vps74).

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Section: A Genomewide Screen Identified 89 Opimentioning

confidence: 99%

Section: A Genomewide Screen Identified 89 Opimentioning

confidence: 99%

Genomic Analysis of the Opi− Phenotype

2006

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“…In opil cells, the ZNOl transcript fails to be repressed in exponential phase in response to inositol and choline (Hirsch & Henry, 1986). In wildtype cells, the level of ZNOl mRNA is also affected by the levels of CDP-diacylglycerol synthase activity (Shen & Dowhan, 1997). Similarly, the ZNOl gene is repressed upon entry into stationary phase even when inositol and choline are absent from the growth medium (Lamping et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic effects of the opil regulatory mutation of yeast: its effects on growth and on phospholipid and inositol metabolism

1998

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Key factors which impact on the biosynthesis and subsequent fate of the phospholipid precursor inositol were studied as a function of growth phase in the yeast Sacchammyces cerevisiae. Both wild-type and strains disrupted for the OPI7 gene, the principal negative regulator of the phospholipid biosynthetic genes, were examined. Overexpression of the IN07 gene and overproduction of both inositol and the major inositol-containing phospholipid, phosphatidylinositol. varied as a function of growth phase. In Opi7 cells, IN07 expression was constitutive at a high level throughout growth, although the level of transcript was reduced at stationary phase when the cells were grown in defined medium. In the wild-type strain, IN07 expression was limited to a peak in the exponential phase of growth in cells grown in the absence of inositol. Interestingly, the pattern of OW7 expression in the wildtype strain resembled that of its putative target, IN07. lntracellular inositol contents of the opi7 strain were higher than those of the wild-type strain. with peak levels occurring in the stationary phase. Membrane phosphatidylinositol content paralleled intracellular inositol content, with opil strains having a higher phosphatidylinositol content in stationary phase. The proportion of the predominant phospholipid, phosphatidylcholine, exhibited a profile that was the inverse of the phosphatidylinositol content: phosphatidylcholine content was lowest in Opi7 cells in stationary phase. The Opil mutation was also found to have effects beyond phospholipid biosynthesis. opi7 cells were smaller, and Opi7 cultures achieved a cell density twice as high as comparable wild-type cultures. Opil cells were also more salt tolerant than wild-type cells: they were partly resistant to shrinking, more rapidly resumed growth, and attained a higher culture density after upshift to medium supplemented with 8 % NaCl.

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“…A high level of CDP-DAG synthase activity favours synthesis of PtdIns over PtdSer. 234 Cells expressing low levels of Cds1p excrete inositol into the medium. 233 CDP-DAG synthase levels, and hence CDP-DAG levels, affect the transcription of the INO1 and CHO1/PSS1 genes independent of the expression of the regulator genes INO2 and INO4 or the inositol/choline levels in the medium.…”

Section: Phospholipid Synthesismentioning

confidence: 99%

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Daum

Lees

Bard

et al. 1998

Yeast

580

380

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The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross‐talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes. © 1998 John Wiley & Sons, Ltd.

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Regulation of Phospholipid Biosynthetic Enzymes by the Level of CDP-Diacylglycerol Synthase Activity

Cited by 41 publications

References 43 publications

Genomic Analysis of the Opi− Phenotype

Genomic Analysis of the Opi− Phenotype

Pleiotropic effects of the opil regulatory mutation of yeast: its effects on growth and on phospholipid and inositol metabolism

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

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