Positive and negative transcriptional control by heme of genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae.

Thorsness, Mary K.; Schafer, William R.; D'Ari, Linda; Rine, Jasper

doi:10.1128/mcb.9.12.5702

Cited by 91 publications

(88 citation statements)

References 55 publications

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“…28 However, these studies were conducted before the demonstration of two isoforms of the enzyme. Thorsness et al 259 have found that HMG1 expression was stimulated by heme while HMG2 expression was inhibited, again indicating a relationship between heme and sterol biosynthesis.…”

Section: Sterol Biosynthesis: Acetate To Farnesyl Pyrophosphatementioning

confidence: 99%

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Daum

Lees

Bard

et al. 1998

Yeast

579

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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Section: Sterol Biosynthesis: Acetate To Farnesyl Pyrophosphatementioning

confidence: 99%

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Daum

Lees

Bard

et al. 1998

Yeast

579

380

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“…Microscopic examination revealed that the inviable spores did not germinate. We therefore conclude that the Cells were lysed by vortexing in the presence of glass beads (Thorsness et al, 1989) and a 50-70% (NH 4 ) 2 SO 4 fraction was used as the source of enzyme (Hossain and Kallenbach, 1974). The kinetics of tRNA-dependent incorporation of 3 H-labeled tryptophan (TRP) into trichloroacetic acid-insoluble material was measured as a function of protein (Yesland and Johnson, 1993).…”

Section: Resultsmentioning

confidence: 99%

Identification and Expression of theSaccharomyces cerevisiae Cytoplasmic Tryptophanyl-tRNA Synthetase Gene

John

Ghosh

Johnson

1997

Yeast

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The enzymes that aminoacylate tRNAs have been studied extensively and can be organized into two distinct classes based on signature sequences and the position of aminoacylation. The class I enzymes have canonical HIGH and KMSKS sequences as part of a Rossman fold nucleotide‐binding site. The tryptophan‐specific enzymes have been placed in class I based on analysis of the cognate genes from Escherichia coli, B. stearothermophilus, B. taurus, and Homo sapiens. An unidentified open reading frame (ORF) on Saccharomyces cerevisiae chromosome XV, HRE342, has 46% identity with the bovine tryptophanyl‐tRNA synthetase and possesses the appropriate signature sequences. The predicted molecular weight of the putative HRE342 protein also closely matched the expected monomer size of the S. cerevisiae enzyme. The HRE342 ORF plus about 250 bp of 5′ and 3′ flanking sequence was amplified by polymerase chain reaction, cloned into a 2 μ based vector, and transformed into a host strain, S. cerevisiae JG369.3B. Nucleotide sequence analysis of the clone confirmed the presence of HRE342. Extracts from transformed yeast have a 30‐ to 100‐fold increase in specific activity of the tryptophanyl‐tRNA synthetase. An HRE342 locus in a diploid strain, PTY33XPTY44, was disrupted with a LEU2 insert. Sporulation and tetrad analysis of the HRE342::LEU2 strain demonstrated that HRE342 is an essential gene. We conclude that HRE342 is the S. cerevisiae gene encoding the cytoplasmic tryptophanyl‐tRNA synthetase, WRS1. A search of the Saccharomyces Genome Database using amino acid sequences from other eukaryotic aminoacyl‐tRNA synthetases suggests there is sufficient similarity to identify both class I and class II genes. © 1997 by John Wiley & Sons, Ltd.

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“…Hem14p converts protoporphyrinogen IX to protoporphyrin IX in the late step of heme synthesis (28,29), so in ⌬hem14 cells, the function of heme-containing proteins such as the ergosterol synthesis-related enzymes Erg5p and Erg11p (36,37) would be reduced. Moreover, the expression of HMG1 and ERG11, regulated by heme at the transcriptional level (32,33), would be also decreased. Finally, Kes1p, an oxysterol-binding protein homolog, is thought to be involved in ergosterol transport from the Golgi to the plasma membrane, and although total ergosterol levels in ⌬kes1 cells are unchanged, the levels on the cell surface are reduced (38).…”

Section: Discussionmentioning

confidence: 99%

“…Hmg1p is involved in the synthesis of farnesyl diphosphate (30), which is also required for synthesis of certain hemes (hemes O and A) (31). Some genes involved in ergosterol biosynthesis, including HMG1 and ERG11, are regulated by heme at the transcriptional level (32,33), and the transcription factor Hap1p is known to be involved in this regulation (34).…”

Section: Phs Sensitivity In the Mutants Of Identified Genes-wementioning

confidence: 99%

Regulation of the Sphingoid Long-chain Base Kinase Lcb4p by Ergosterol and Heme

Sano

Kihara

Kurotsu

et al. 2005

Journal of Biological Chemistry

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Sphingoid long-chain base 1-phosphates (LCBPs) are widely conserved, bioactive lipid molecules. In yeast, LCBPs are known to be involved in several cellular responses such as heat shock resistance and Ca 2؉ mobilization, although their target molecules and signaling pathways remain unclear. To identify genes involved in LCBP signaling and in regulation of LCBP synthesis, we performed transposon mutagenesis in cells lacking the LCBP lyase DPL1 and LCBP phosphatase LCB3 genes and screened for phytosphingosine-resistant clones. Further isolation and identification revealed eight genes (PBP1, HEM14, UFD4, HMG1, TPS1, KES1, WHI2, and ERG5), in addition to the previously characterized LCB4 and PDR5 genes, that are involved in phytosphingosine resistance. Of these eight, four are ergosterol-related genes (HEM14, HMG1, KES1, and ERG5). We also demonstrated that protein expression of the long-chain base kinase Lcb4p was reduced in ⌬hem14 and ⌬hmg1 cells, likely as a consequence of decreased activity of the heme-dependent transcription factor Hap1p. In addition, phosphorylation of Lcb4p was decreased in all the ergosterol-related mutants isolated and other ergosterol mutants constructed (⌬erg2, ⌬erg3, and ⌬erg6). Finally, plasma membrane localization of Lcb4p was found to be reduced in ⌬erg6 cells. These results suggest that changes in sterol composition affect the phosphorylation of Lcb4p because of the altered localization. The other genes isolated (PBP1, UFD4, TPS1, and WHI2) may be involved in LCBP signaling.Sphingolipids are major membrane components of eukaryotic cells. Ceramide, the backbone of sphingolipids, is formed by the amide linkage of a sphingoid long-chain base (LCB) 2 with a fatty acid. The major mammalian LCB is sphingosine, whereas in the yeast Saccharomyces cerevisiae, dihydrosphingosine (DHS) and phytosphingosine (PHS) serve as LCBs. LCBs are bioactive lipid molecules involved in apoptosis, endocytosis, and G 1 cell cycle arrest (1-3). The phosphorylation of LCBs at C-1 results in the production of long-chain base 1-phosphates (LCBPs), sphingosine 1-phosphate (S1P) in mammals and PHS 1-phosphate (PHS1P) and DHS 1-phosphate in yeast. Interestingly, LCBPs possess completely different biological functions compared with the original LCBs.In mammalian cells, S1P is known to elicit various cellular responses via the cell-surface SIP/Edg (endothelial differentiation gene) receptors, such as proliferation, motility, differentiation, and immunity (4 -7). In addition to its role as an extracellular signal mediator, S1P also functions intracellularly. Intracellular S1P has been proposed to be involved in Ca 2ϩ mobilization, cell proliferation, G 1 /S cell cycle transition, and inhibition of apoptosis (4 -7), although its intracellular target molecules and signaling pathways remain unclear.Because yeast cells do not possess a cell-surface receptor for LCBP/ S1P, their LCBPs function only intracellularly (8 -11). Yeast LCBPs and mammalian intracellular S1P share some effects. For instance, both influence Ca 2ϩ mob...

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Positive and negative transcriptional control by heme of genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae.

Cited by 91 publications

References 55 publications

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Identification and Expression of theSaccharomyces cerevisiae Cytoplasmic Tryptophanyl-tRNA Synthetase Gene

Regulation of the Sphingoid Long-chain Base Kinase Lcb4p by Ergosterol and Heme

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