The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance.

Bailis, Adam M.; Poole, M. A.; Carman, George M.; Henry, Susan A.

doi:10.1128/mcb.7.1.167

Cited by 119 publications

(118 citation statements)

References 53 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Not only was the degree of repression of certain genes enhanced but also a greater number of genes were found to be differentially expressed in the presence of both precursors. This is in agreement with previous reports measuring expression of individual genes, including INO1 (16), CHO1 (17,20), OP13 (21), CKI1 (52). We also show for the first time that ITR1, YEL073C, YIP3, PSD1, and SAH1 match this pattern of regulation.…”

Section: Analysis Of Genome-wide Expression Regulated By Inositolsupporting

confidence: 93%

“…For example, it was originally reported that INO1 expression is repressed by an additional 2-3-fold in cells grown in inositol-containing medium when choline is present compared with cells grown in inositol-containing medium when choline is absent (16). Similar simultaneous effects of inositol and choline have also been observed for CHO1 (17,20), OP13 (21), CHO2 (21), CKI1 (52), and CPT1 (53). All of the above genes have been shown to contain an active UAS INO element in their promoters, suggesting that the additive repressive effect of choline in the presence of inositol might be specific to this particular set of genes.…”

Section: Global Analysis Of Inositol and Choline On Gene Expressionmentioning

confidence: 56%

“…The current study (Table II) and previous studies (55,72) showed that INO2 expression is down-regulated in the presence of inositol, which is present in YPD media. Moreover, CKI1, HMN1, and CHO1 each contain a UAS INO element in their promoters (1) and match the pattern of regulation of other UAS INO -containing genes (17,20,52,54). Thus, it is likely that both Ino2p and Ino4p are required for their regulated expression.…”

Section: Analysis Of Genome-wide Expression Regulated By Inositolmentioning

confidence: 99%

See 2 more Smart Citations

Genome-wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

Jesch

Zhao

Wells

et al. 2005

Journal of Biological Chemistry

118

194

View full text Add to dashboard Cite

In the yeast Saccharomyces cerevisiae, the transcription of many genes encoding enzymes of phospholipid biosynthesis are repressed in cells grown in the presence of the phospholipid precursors inositol and choline. A genome-wide approach using cDNA microarray technology was used to profile the changes in the expression of all genes in yeast that respond to the exogenous presence of inositol and choline. We report that the global response to inositol is completely distinct from the effect of choline. Whereas the effect of inositol on gene expression was primarily repressing, the effect of choline on gene expression was activating. Moreover, the combination of inositol and choline increased the number of repressed genes compared with inositol alone and enhanced the repression levels of a subset of genes that responded to inositol. In all, 110 genes were repressed in the presence of inositol and choline. Two distinct sets of genes exhibited differential expression in response to inositol or the combination of inositol and choline in wild-type cells. One set of genes contained the UAS INO sequence and were bound by Ino2p and Ino4p. Many of these genes were also negatively regulated by OPI1, suggesting a common regulatory mechanism for Ino2p, Ino4p, and Opi1p. Another nonoverlapping set of genes was coregulated by the unfolded protein response pathway, an ER-localized stress response pathway, but was not dependent on OPI1 and did not show further repression when choline was present together with inositol. These results suggest that inositol is the major effector of target gene expression, whereas choline plays a minor role.Phospholipids are the key structural elements of membranebounded organelles and play important roles in signaling and membrane trafficking pathways. Each membrane compartment is composed of a unique set of phospholipids whose biophysical properties contribute to the function of each organelle. Phospholipid metabolism is highly regulated by the cell, ensuring the biogenesis and growth of membranes by coordinating the relative rates of synthesis of individual phospholipids with numerous factors, such as the availability of exogenous supplies of phospholipid precursors, growth stage, and membrane trafficking (1, 2).

show abstract

Section: Analysis Of Genome-wide Expression Regulated By Inositolsupporting

confidence: 93%

Section: Global Analysis Of Inositol and Choline On Gene Expressionmentioning

confidence: 56%

Section: Analysis Of Genome-wide Expression Regulated By Inositolmentioning

confidence: 99%

See 1 more Smart Citation

Genome-wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

Jesch

Zhao

Wells

et al. 2005

Journal of Biological Chemistry

118

194

View full text Add to dashboard Cite

show abstract

“…CHO1 expression is regulated by water-soluble phospholipid precursors (e.g. inositol supplementation) (59,90,94,95) and by growth phase (96,97). The activity of PS synthase is modulated by membrane phospholipids (98 -100) and is inhibited by inositol (101) and by CTP (39).…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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...

show abstract

“…Inositol is a key regulator of the enzymes required for inositol and phospholipid biosynthesis. Regulation of many of these enzymes by inositol occurs at the level of transcript abundance (Bailis et al, 1987;White et al, 1991). The products of three regulatory genes bring about inositol-mediated regulation, including the positive regulators INO2 and INO4 and the negative regulator OPI1 (Klig et al, 1988;Nikoloff et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Regulation of inositol monophosphatase in Saccharomyces cerevisiae

Murray

Greenberg

1997

Molecular Microbiology

View full text Add to dashboard Cite

SummaryInositol monophosphatase is a key enzyme in the de novo biosynthesis of inositol and in the phosphoinositide second-messenger signalling pathway. Inhibition of this enzyme is a proposed mechanism for lithium's pharmacological action in bipolar illness (manic depression). Very little is known about how expression of this enzyme is regulated. Because the yeast Saccharomyces cerevisiae has been shown to be an excellent model system in which to understand the regulation of inositol metabolism, we characterized inositol monophosphatase in this yeast. Lithium inhibited monophosphatase activity in vitro. Growth in the presence of inositol resulted in increased expression of the enzyme in vivo, although inositol had no effect on enzyme activity in vitro. The inositol effect was apparent when cells were grown in glucose but not in glycerol/ethanol. Monophosphatase activity was derepressed as cells entered stationary phase. This effect was apparent only during growth in glucose plus inositol. The results demonstrate that S. cerevisiae monophosphatase is inhibited by lithium and regulated by factors affecting phospholipid biosynthesis.

show abstract

The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance.

Cited by 119 publications

References 53 publications

Genome-wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

Genome-wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

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

Regulation of inositol monophosphatase in Saccharomyces cerevisiae

Contact Info

Product

Resources

About