NTE1-encoded Phosphatidylcholine Phospholipase B Regulates Transcription of Phospholipid Biosynthetic Genes

Fernández-Murray, J. Pedro; Gaspard, Gerard J.; Jesch, Stephen A.; McMaster, Christopher R.

doi:10.1074/jbc.m109.063958

Cited by 36 publications

(36 citation statements)

References 60 publications

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“…More work is necessary to understand impaired derepression of phospholipid synthesis genes in orm1Δ orm2Δ cells. A recent report suggests that lipid packing within membranes can regulate derepression of phospholipid gene transcription (28).…”

Section: Discussionmentioning

confidence: 99%

Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control

Han

Lone

Schneiter

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

261

290

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Yeast members of the ORMDL family of endoplasmic reticulum (ER) membrane proteins play a central role in lipid homeostasis and protein quality control. In the absence of yeast Orm1 and Orm2, accumulation of long chain base, a sphingolipid precursor, suggests dysregulation of sphingolipid synthesis. Physical interaction between Orm1 and Orm2 and serine palmitoyltransferase, responsible for the first committed step in sphingolipid synthesis, further supports a role for the Orm proteins in regulating sphingolipid synthesis. Phospholipid homeostasis is also affected in orm1 Δ orm2 Δ cells: the cells are inositol auxotrophs with impaired transcriptional regulation of genes encoding phospholipid biosynthesis enzymes. Strikingly, impaired growth of orm1 Δ orm2 Δ cells is associated with constitutive unfolded protein response, sensitivity to stress, and slow ER-to-Golgi transport. Inhibition of sphingolipid synthesis suppresses orm1 Δ orm2 Δ phenotypes, including ER stress, suggesting that disrupted sphingolipid homeostasis accounts for pleiotropic phenotypes. Thus, the yeast Orm proteins control membrane biogenesis by coordinating lipid homeostasis with protein quality control.

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Section: Discussionmentioning

confidence: 99%

Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control

Han

Lone

Schneiter

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

261

290

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“…The lipid regulatory transcription factor Opi1p (Greenberg et al 1982) regulates the filamentous growth MAPK pathway . The serine esterase Nte1p, which serves as the phospholipase B of yeast (Fernandez-Murray et al 2009) was also found to regulate the filamentous growth MAPK pathway ( Figure 3F). Ncr1p, which regulates sphingolipid biosynthesis (Malathi et al 2004) and has not been shown to interact with Opi1p or Nte1p genetically or physically, negatively regulated the filamentous growth MAPK pathway.…”

Section: Functional Analysis Of Candidate Genes and Pathwaysmentioning

confidence: 96%

Global Regulation of a Differentiation MAPK Pathway in Yeast

Chavel

Caccamise

Li³

et al. 2014

Genetics

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Cell differentiation requires different pathways to act in concert to produce a specialized cell type. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth in response to nutrient limitation. Differentiation to the filamentous cell type requires multiple signaling pathways, including a mitogen-activated protein kinase (MAPK) pathway. To identify new regulators of the filamentous growth MAPK pathway, a genetic screen was performed with a collection of 4072 nonessential deletion mutants constructed in the filamentous (S1278b) strain background. The screen, in combination with directed gene-deletion analysis, uncovered 97 new regulators of the filamentous growth MAPK pathway comprising 40% of the major regulators of filamentous growth. Functional classification extended known connections to the pathway and identified new connections. One function for the extensive regulatory network was to adjust the activity of the filamentous growth MAPK pathway to the activity of other pathways that regulate the response. In support of this idea, an unregulated filamentous growth MAPK pathway led to an uncoordinated response. Many of the pathways that regulate filamentous growth also regulated each other's targets, which brings to light an integrated signaling network that regulates the differentiation response. The regulatory network characterized here provides a template for understanding MAPK-dependent differentiation that may extend to other systems, including fungal pathogens and metazoans.

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“…As shown in Fig. 2, NTE1 encodes the serine esterase responsible for, among other things, repression of the OPI1-encoded Opi1 repressor protein (Fernández-Murray et al, 2009). The enzyme silences the yeast fatty acid synthase, helping modulate phospholipid biosynthesis in S. cerevisiae (Schweizer and Hofmann, 2004).…”

Section: In Silico Prediction Of Pathway Gene Knockouts Via Optknockmentioning

confidence: 99%

Metabolic engineering of Saccharomyces cerevisiae for the production of triacetic acid lactone

Cárdenas

Silva

2014

Metabolic Engineering

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a b s t r a c tBiobased chemicals have become attractive replacements for their fossil-fuel counterparts. Recent studies have shown triacetic acid lactone (TAL) to be a promising candidate, capable of undergoing chemical conversion to sorbic acid and other valuable intermediates. In this study, Saccharomyces cerevisiae was engineered for the high-level production of TAL by overexpression of the Gerbera hybrida 2-pyrone synthase (2-PS) and systematic engineering of the yeast metabolic pathways. Pathway analysis and a computational approach were employed to target increases in cofactor and precursor pools to improve TAL synthesis. The pathways engineered include those for energy storage and generation, pentose biosynthesis, gluconeogenesis, lipid biosynthesis and regulation, cofactor transport, and fermentative capacity. Seventeen genes were selected for disruption and independently screened for their effect on TAL production; combinations of knockouts were then evaluated. A combination of the pathway engineering and optimal culture parameters led to a 37-fold increase in titer to 2.2 g/L and a 50-fold increase in yield to 0.13 (g/g glucose). These values are the highest reported in the literature, and provide a 3-fold improvement in yield over previous reports using S. cerevisiae. Identification of these metabolic bottlenecks provides a strategy for overproduction of other acetyl-CoA-dependent products in yeast.

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NTE1-encoded Phosphatidylcholine Phospholipase B Regulates Transcription of Phospholipid Biosynthetic Genes

Cited by 36 publications

References 60 publications

Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control

Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control

Global Regulation of a Differentiation MAPK Pathway in Yeast

Metabolic engineering of Saccharomyces cerevisiae for the production of triacetic acid lactone

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