Stereochemically distinct roles for sterol in Saccharomycescerevisiae

Pinto, William J.; Lozano, Ruben; Sekula, Bernard C.; Nes, William R.

doi:10.1016/0006-291x(83)91795-3

Cited by 54 publications

(24 citation statements)

References 21 publications

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“…It performs many crucial roles within the cell, including maintaining membrane fluidity and integrity by generally allowing lipids, membrane-spanning proteins, or membrane-associated proteins to function properly (159). Ergosterol also contributes specifically to the regulation of cell growth and proliferation (206,211,217,218). Many drugs developed to specifically inhibit fungal growth target its biosynthesis (see below).…”

Section: Regulation Of Ergosterol Biosynthesismentioning

confidence: 99%

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

MacPherson¹,

Larochelle²,

Turcotte

2006

Microbiol Mol Biol Rev

511

554

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SUMMARY The trace element zinc is required for proper functioning of a large number of proteins, including various enzymes. However, most zinc-containing proteins are transcription factors capable of binding DNA and are named zinc finger proteins. They form one of the largest families of transcriptional regulators and are categorized into various classes according to zinc-binding motifs. This review focuses on one class of zinc finger proteins called zinc cluster (or binuclear) proteins. Members of this family are exclusively fungal and possess the well-conserved motif CysX2CysX6CysX5-12CysX2CysX6-8Cys. The cysteine residues bind to two zinc atoms, which coordinate folding of the domain involved in DNA recognition. The first- and best-studied zinc cluster protein is Gal4p, a transcriptional activator of genes involved in the catabolism of galactose in the budding yeast Saccharomyces cerevisiae. Since the discovery of Gal4p, many other zinc cluster proteins have been characterized; they function in a wide range of processes, including primary and secondary metabolism and meiosis. Other roles include regulation of genes involved in the stress response as well as pleiotropic drug resistance, as demonstrated in budding yeast and in human fungal pathogens. With the number of characterized zinc cluster proteins growing rapidly, it is becoming more and more apparent that they are important regulators of fungal physiology.

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Section: Regulation Of Ergosterol Biosynthesismentioning

confidence: 99%

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

MacPherson¹,

Larochelle²,

Turcotte

2006

Microbiol Mol Biol Rev

511

554

View full text Add to dashboard Cite

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“…Nes and colleagues tested the ability of different exogenous sterols to promote the growth of cells unable to synthesize their own sterols and found only sterols that contain C-28 methyl groups to be effective (20,21). However, in these experiments the synthesis of both heme and sterols was blocked, as the cells were grown anaerobically in the presence of a metabolic inhibitor of squalene cyclase in order to induce uptake of exogenous sterols.…”

Section: Discussionmentioning

confidence: 99%

“…They reported that only sterols possessing the C-5,6 double bond (e.g., ergosterol) or, similarly, those capable of being desaturated at C-5 fulfill the sparking requirement. On the other hand, Nes and colleagues used anaerobiosis and an inhibitor of squalene cyclase to induce exogenous sterol dependency and suggested that under these conditions growth is dependent on sterols that possess the C-28 methyl group (20,21). The enzymatic modifications of sterol that give rise to ergosterol-specific structural features are excellent targets for mutational studies.…”

mentioning

confidence: 99%

The yeast gene ERG6 is required for normal membrane function but is not essential for biosynthesis of the cell-cycle-sparking sterol.

Gaber¹,

Copple²,

Kennedy³

et al. 1989

Mol. Cell. Biol.

240

220

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In Saccharomyces cerevisiae, methylation of the principal membrane sterol at C-24 produces the C-28 methyl group specific to ergosterol and represents one of the few structural differences between ergosterol and cholesterol. C-28 in S. cerevisiae has been suggested to be essential for the sparking function (W. J. Pinto and W. R. Nes, J. Biol. Chem. 258:4472-4476, 1983), a cell cycle event that may be required to enter G1 (C. Dahl, H.-P. Biemann, and J. Dahl, Proc. Natl. Acad. Sci. USA 84:4012-4016, 1987). The sterol biosynthetic pathway in S. cerevisiae was genetically altered to assess the functional role of the C-28 methyl group of ergosterol. ERG6, the putative structural gene for S-adenosylmethionine: delta 24-methyltransferase, which catalyzes C-24 methylation, was cloned, and haploid strains containing erg6 null alleles (erg6 delta 1 and erg6 delta ::LEU2) were generated. Although erg6 delta cells are unable to methylate ergosterol precursors at C-24, they exhibit normal vegatative growth, suggesting that C-28 sterols are not essential in S. cerevisiae. However, erg6 delta cells exhibit pleiotropic phenotypes that include defective conjugation, hypersensitivity to cycloheximide, resistance to nystatin, a severely diminished capacity for genetic transformation, and defective tryptophan uptake. These phenotypes reflect the role of ergosterol as a regulator of membrane permeability and fluidity. Genetic mapping experiments revealed that ERG6 is located on chromosome XIII, tightly linked to sec59.

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“…In addition, we have demonstrated the phenomenon of sterol synergism or sparing in this simple eukaryote, i.e. the adequacy of non-growth-supporting sterols for the cell's bulk membrane structural requirement when a much lower concentration of an essential phytosterol is provided to meet the nutritional requirement (Pinto et al, 1983;Rampogal & Bloch, 1983;Whitaker & Nelson, 1987).…”

Section: Introductionmentioning

confidence: 94%

Sterol Synergism in Paramecium tetraurelia

Whitaker

Nelson

1988

Microbiology

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Paramecium tetraurelia is a naturally occurring sterol auxotroph with an absolute nutritional requirement for one of a small group of structurally related phytosterols. We report here a quantitative study demonstrating that a low, otherwise sub-supportive, concentration ( x 0.020-0.050 pg ml-l) of an essential phytosterol (stigmasterol) is adequate for growth of this ciliate, provided that a second, relatively non-specific sterol is available at a higher concentration (1.0p.g ml-*) to allow for membrane biosynthesis. This phenomenon, referred to as sterol synergism, has been observed in a broad taxonomic range of organisms, with the conclusion that small amounts of specific sterols are required to perform some previously unknown, vital metabolic or regulatory function. Paramecium promises to be an excellent model organism for the elucidation of essential sterol function.

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Stereochemically distinct roles for sterol in Saccharomycescerevisiae

Cited by 54 publications

References 21 publications

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

The yeast gene ERG6 is required for normal membrane function but is not essential for biosynthesis of the cell-cycle-sparking sterol.

Sterol Synergism in Paramecium tetraurelia

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