Salt tolerance and methionine biosynthesis in Saccharomyces cerevisiae involve a putative phosphatase gene.

Gläser, Heinz-U.; Thomas, Dominique; Gaxiola, Roberto A.; Montrichard, Françoise; Surdin-Kerjan, Yolande; Serrano, Ramón

doi:10.1002/j.1460-2075.1993.tb05979.x

Cited by 140 publications

(175 citation statements)

References 38 publications

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“…1. The seven members that were used for calculation included SuhB, bovine inositol monophosphatase (4), CysQ (which is involved in sulfate assimilation in E. coli) (25), Qut-G and Qa-X (which are hypothetical gene products from open reading frames in Aspergillus nidulans and Neurospora crassa, respectively) (8,12), bovine inositol polyphosphate 1-phosphatase (which hydrolyzes the 1-position phosphate of inositol 1,3,4-triphosphate and inositol 1,4-bisphosphate) (41), and Met22 (which is involved in salt tolerance in Saccharomyces cerevisiae) (9). Not only do these proteins share two sequence motifs (26), but the similarity is found throughout the length of the SuhB sequence (except for long insertions in inositol polyphosphate 1-phosphatase, Met22, Qut-G, and Qa-X).…”

Section: Resultsmentioning

confidence: 99%

“…3.25) hydrolyzes the ester bond of myo-inositol 1(or 4)-phosphate to release myo-inositol plus P i and plays a key role in the biosyntheses of inositol phosphates and inositol phospholipids that are involved in signal transduction in mammalian and plant cells (for reviews, see references 5 and 21). Genes homologous to inositol monophosphatase have been identified in bacteria, lower eukaryotes, and higher eukaryotes (9,26), indicating that this family of genes has evolved in diverse ways from a common ancestral gene that may have originated before the separation of eukaryotes and prokaryotes.…”

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confidence: 99%

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Inositol monophosphatase activity from the Escherichia coli suhB gene product

et al. 1995

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The suhB gene is located at 55 min on the Escherichia coli chromosome and encodes a protein of 268 amino acids. Mutant alleles of suhB have been isolated as extragenic suppressors for the protein secretion mutation (secY24), the heat shock response mutation (rpoH15), and the DNA synthesis mutation (dnaB121) (K. Shiba, K. Ito, and T. Yura, J. Bacteriol. 160:696-701, 1984; R. Yano, H. Nagai, K. Shiba, and T. Yura, J. Bacteriol. 172:2124-2130, 1990; S. Chang, D. Ng, L. Baird, and C. Georgopoulos, J. Biol. Chem. 266:3654-3660, 1991). These mutant alleles of suhB cause cold-sensitive cell growth, indicating that the suhB gene is essential at low temperatures. Little work has been done, however, to elucidate the role of the product of suhB in a normal cell and the suppression mechanisms of the suhB mutations in the aforementioned mutants. The sequence similarity shared between the suhB gene product and mammalian inositol monophosphatase has prompted us to test the inositol monophosphatase activity of the suhB gene product. We report here that the purified SuhB protein showed inositol monophosphatase activity. The kinetic parameters of SuhB inositol monophosphatase (K m ‫؍‬ 0.071 mM; V max ‫؍‬ 12.3 mol/min per mg) are similar to those of mammalian inositol monophosphatase. The ssyA3 and suhB2 mutations, which were isolated as extragenic suppressors for secY24 and rpoH15, respectively, had a DNA insertion at the 5 proximal region of the suhB gene, and the amount of SuhB protein within mutant cells decreased. The possible role of suhB in E. coli is discussed.The suhB gene was first identified as the locus for the ssyA3(Cs) mutation that was isolated as an extragenic suppressor for the secY24(Ts) mutant (31). The ssyA3 mutation restored the defect in protein secretion caused by the secY24 mutation (33) and rescued the temperature-sensitive cell growth of secY24 mutant cells. The ssyA3 mutation caused cold-sensitive cell growth by itself and impaired protein synthesis was observed in the ssyA3 mutant at low temperatures (31). The cold-sensitive growth of the ssyA3 mutant was rescued by introduction of the wild-type copy of suhB, indicating that ssyA3 is a mutant allele of suhB (40). The suhB2(Cs) mutation is another allele of suhB and was isolated as an extragenic suppressor of the rpoH15(Ts) mutation. The rpoH15 mutant gene produces an altered 32 protein and causes a defect in the induction of heat shock proteins at higher temperatures (42). The suhB2(Cs) mutation rescued the temperature-sensitive cell growth of the rpoH15 mutant and partially restored heat shock induction in the mutant cell (40). A coldsensitive mutation was also mapped in the suhB locus as an extragenic suppressor for the dnaB121(Ts) mutation that inhibits replication of phage (2). Thus, mutant alleles of suhB have effects on diverse cell activities, including protein export, stress response, and DNA replication.The suhB gene encodes a protein of 268 amino acids (40), and the primary structure of its translated product shows a high level of similarity t...

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Section: Resultsmentioning

confidence: 99%

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Inositol monophosphatase activity from the Escherichia coli suhB gene product

et al. 1995

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“…The ena1,2,3,4 strain was used to avoid the complex regulatory system of this major determinant of salt tolerance , whereas methionine supplementation bypasses the salt-sensitive HAL2-methionine pathway (Glä ser et al, 1993). The use of lithium as the toxic cation instead of sodium offered the advantage that this cation inhibits growth at concentrations low enough to pose no osmotic problems.…”

Section: Nst1/ynl091w Is a Negative Factor For Salt Tolerancementioning

confidence: 99%

“…Hal2p is a specific phosphatase acting on 3k-phosphoadenosine-5k-phosphate (PAP) and sensitive to inhibition by physiological concentrations of sodium. PAP accumulation during salt stress inhibits sulphate assimilation into methionine (Glä ser et al, 1993) and RNA processing (Dichtl et al, 1997) and this accounts for part of salt toxicity.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Nst1p/YNL091w and Msl1p, a U2B″ splicing factor, in Saccharomyces cerevisiae salt tolerance

Goossens¹,

Forment²,

Serrano³

2002

Yeast

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Cell tolerance to salt stress depends on many physiological functions, including the best characterized of osmotic adjustment, ion transport and sodium-sensitive sulphate metabolism. From a screening designed to identify novel determinants of salt tolerance we have isolated the YNL091w gene, probably an Ascomycete-specific gene encoding a protein of unknown function. This gene negatively affects salt tolerance and therefore has been designated NST1. The salt tolerance mechanism of nst1 mutants is novel because it is not related to osmoregulation, altered cation accumulation or sulphate metabolism. Genome-wide two-hybrid analysis has suggested that Nst1p interacts with the splicing factor Msl1p and, accordingly, the impact of NST1 on salt tolerance is dependent on a functional MSL1 gene. Loss of MSL1 and NST1 function has pleiotropic phenotypes including increased sensitivity to divalent cations (manganese and zinc) and to caffeine (a cell wall-weakening agent). On the other hand, msl1 mutants but not nst1 mutants are sensitive to thiabendazole (a microtubule-destabilizing agent) and to osmotic stress.

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“…Zuker and colleagues provided genetic evidence in Drosophila melanogaster that the loss of INPP1 phenocopies lithium's alteration of neuromuscular junction physiology (10). In yeast, bisphosphate 3Јnucleotidase activity (encoded by MET22, also known as HAL2) has been linked to the cellular toxicity of lithium (11)(12)(13)(14). Met22/Hal2 is functionally orthologous to BPNT1, having 3Ј-nucleotidase activity toward 3Ј-phosphoadenosine 5Ј-phosphate (PAP) and 3Ј-phosphoadenosine 5Ј-phosphosulfate (PAPS), and it is a key regulator of the sulfur assimilation pathway (Fig.…”

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Alteration of Lithium Pharmacology through Manipulation of Phosphoadenosine Phosphate Metabolism

Spiegelberg¹,

Cruz

Law

et al. 2005

Journal of Biological Chemistry

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Bisphosphate 3 -nucleotidase (BPNT1 in mammals and Met22/Hal2 in yeast) is one of five members of a family of signaling phosphatases united through a common tertiary structure and inhibition by subtherapeutic doses of the antibipolar drug lithium. Here we report a role for 3 -nucleotidase and its substrate, 3 -phosphoadenosine 5 -phosphate (PAP), in mediating the cellular effects of lithium. Lithium-induced inhibition of growth in yeast cells may be overcome by dose-dependent heterologous expression of human BPNT1. Disruption of the yeast 3 -nucleotidase gene or treatment of cells with lithium results in a >80-fold accumulation of PAP and leads to potent growth inhibition. These data indicate that the accumulation of a 3 -nucleotidase substrate, such as PAP, mediates the toxicity of lithium. To further probe this model we examined the growth inhibitory effects of lithium under conditions in which PAP biosynthetic machinery was concomitantly down-regulated. Disruption of met3 or met14 genes (ATP sulfurylase or phosphosulfate kinase), transcriptional down-regulation of MET3 through methionine addition, or administration of chlorate, a widely used cell-permeable sulfurylase inhibitor, function to reduce lithium-induced intracellular PAP accumulation and lithium toxicity; all of these effects were reversed by heterologous expression of human sulfurylase and kinase. Collectively, our data support a role for 3 -nucleotidase activity and PAP metabolism in aspects of lithium's mechanism of action and provide a platform for development of novel pharmacological modulators aimed at improving therapies for the treatment of bipolar disorder.Lithium has been widely used for over 50 years to treat bipolar disorder (manic depressive disease). Despite its success, the mechanisms by which lithium exerts therapeutic and toxic effects remain unclear. Insights into lithium pharmacology have come with the identification of a signaling phosphatase family whose members are inhibited potently by lithium at subtherapeutic concentrations. Family members have relatively weak overall sequence similarities (Ͻ25%) but are unified by a conserved core three-dimensional structure and the conserved pattern motif D(X) n EE(X) n DP(I/L)D(S/G/A)T(X) n -WD(X) 11 GG (1). This motif has been used to identify novel family members, for example human and mouse bisphosphate 3Ј-nucleotidase 1 (BPNT1), 1 through the scanning of emerging genomic databases and "reverse" biochemical characterization of the gene product (2). Importantly BPNT1 is potently inhibited by lithium (2, 3) and, to our knowledge, ranks among the most sensitive lithium targets described in the literature to date, including the glycogen synthase kinase-3 isoforms (4, 5). There are five distinct branches in the complete family of human and mouse signaling phosphatases (Fig. 1A), including inositol monophosphatase (IMP1 and IMP2), inositol polyphosphate 1-phosphatase (INPP1), fructose 1,6-bisphosphatase (FBP1 and FBP2), BPNT1, and a novel gene product (GenBank TM accession number AY032885) d...

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Salt tolerance and methionine biosynthesis in Saccharomyces cerevisiae involve a putative phosphatase gene.

Cited by 140 publications

References 38 publications

Inositol monophosphatase activity from the Escherichia coli suhB gene product

Inositol monophosphatase activity from the Escherichia coli suhB gene product

Involvement of Nst1p/YNL091w and Msl1p, a U2B″ splicing factor, in Saccharomyces cerevisiae salt tolerance

Alteration of Lithium Pharmacology through Manipulation of Phosphoadenosine Phosphate Metabolism

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