Revisiting Purine-Histidine Cross-Pathway Regulation in Saccharomyces cerevisiae

Rébora, Karine; Laloo, Benoît; Daignan‐Fornier, Bertrand

doi:10.1534/genetics.104.039396

Cited by 89 publications

(98 citation statements)

References 39 publications

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“…Indeed, apart from playing a crucial role in the control of phosphate homeostasis, Pho2 together with the transcription factor Bas1 co-regulates the expression of the so-called ADE regulon that includes genes involved in the de novo synthesis of purines (Daignan-Fornier and Fink 1992). Consistently, a recent transcriptome analysis revealed that the metabolic intermediate AICAR (5 0 -phosphoribosyl-5-amino-4-imidazole carboxamide), which was previously identified as a transcriptional regulator of the purine pathway genes (Rebora et al 2001;Rebora et al 2005), also mediates the expression of several PHO genes ). These authors reported that Pho4 and Bas1 compete for Pho2 binding and that AICAR stimulates the interaction between either Pho4 or Bas1 with Pho2.…”

Section: The Protein Kinase Sch9mentioning

confidence: 79%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G 0 ) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.

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Section: The Protein Kinase Sch9mentioning

confidence: 79%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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“…When the ends of the genomic clones were sequenced, all 5 contained genes within an $13-kb region on chromosome 11 in C. glabrata ( Figure 1B). This region contains three paralogs of PMU1, a gene that in S. cerevisiae encodes a phosphomutase-like protein (Elliott et al 1996;Rebora et al 2005;Byrne and Wolfe 2006). Because phosphomutase binds to phosphoglycerate and isomerizes carbon phosphate bonds, it seemed plausible that these proteins might bind to and hydrolyze organic phosphate compounds.…”

Section: Resultsmentioning

confidence: 99%

“…CgPMU2 Is Phosphate Starvation-Inducible Acid Phosphataseauxotrophy of the ade3 ade16 ade17 triple mutant (Rebora et al 2005). The histidine requirement is probably suppressed by detoxifying AICAR, a monophosphate nucleotide derivative (Rebora et al 2005).…”

Section: Resultsmentioning

confidence: 99%

Novel Acid Phosphatase in Candida glabrata Suggests Selective Pressure and Niche Specialization in the Phosphate Signal Transduction Pathway

et al. 2010

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Evolution through natural selection suggests unnecessary genes are lost. We observed that the yeast Candida glabrata lost the gene encoding a phosphate-repressible acid phosphatase (PHO5) present in many yeasts including Saccharomyces cerevisiae. However, C. glabrata still had phosphate starvation-inducible phosphatase activity. Screening a C. glabrata genomic library, we identified CgPMU2, a member of a threegene family that contains a phosphomutase-like domain. This small-scale gene duplication event could allow for sub-or neofunctionalization. On the basis of phylogenetic and biochemical characterizations, CgPMU2 has neofunctionalized to become a broad range, phosphate starvation-regulated acid phosphatase, which functionally replaces PHO5 in this pathogenic yeast. We determined that CgPmu2, unlike ScPho5, is not able to hydrolyze phytic acid (inositol hexakisphosphate). Phytic acid is present in fruits and seeds where S. cerevisiae grows, but is not abundant in mammalian tissues where C. glabrata grows. We demonstrated that C. glabrata is limited from an environment where phytic acid is the only source of phosphate. Our work suggests that during evolutionary time, the selection for the ancestral PHO5 was lost and that C. glabrata neofunctionalized a weak phosphatase to replace PHO5. Convergent evolution of a phosphate starvation-inducible acid phosphatase in C. glabrata relative to most yeast species provides an example of how small changes in signal transduction pathways can mediate genetic isolation and uncovers a potential speciation gene.

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“…Wild-type (WT, BY4742) and amd1 mutant strains were grown in SDcasaW medium supplemented (1Ade) or not (ÀAde) with external adenine. Internal adenylic (B) and guanylic (C) nucleotides were measured as previously described (Breton et al 2008;Gauthier et al 2008). this mutant was due to IMP synthesis via AICAR from the purine and histidine de novo pathways (Rebora et al 2005) (Figure 1) and could be totally abolished in the ade8 his1 aah1 amd1 quadruple mutant ( Figure 3B). As expected, this quadruple mutant was fully viable when hypoxanthine was provided as a purine source ( Figure 3B).…”

Section: Resultsmentioning

confidence: 99%

Phenotypic Consequences of Purine Nucleotide Imbalance inSaccharomyces cerevisiae

et al. 2009

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Coordinating homeostasis of multiple metabolites is a major task for living organisms, and complex interconversion pathways contribute to achieving the proper balance of metabolites. AMP deaminase (AMPD) is such an interconversion enzyme that allows IMP synthesis from AMP. In this article, we show that, under specific conditions, lack of AMPD activity impairs growth. Under these conditions, we found that the intracellular guanylic nucleotide pool was severely affected. In vivo studies of two AMPD homologs, Yjl070p and Ybr284p, indicate that these proteins have no detectable AMP, adenosine, or adenine deaminase activity; we show that overexpression of YJL070c instead mimics a loss of AMPD function. Expression of the yeast transcriptome was monitored in a AMPD-deficient mutant in a strain overexpressing YJL070c and in cells treated with the immunosuppressive drug mycophenolic acid, three conditions that lead to severe depletion of the guanylic nucleotide pool. These three conditions resulted in the up-or downregulation of multiple transcripts, 244 of which are common to at least two conditions and 71 to all three conditions. These transcriptome results, combined with specific mutant analysis, point to threonine metabolism as exquisitely sensitive to the purine nucleotide balance.T HE purine nucleotides, ATP and GTP, are involved in almost all aspects of cellular life. In addition to their role as building blocks of nucleic acids, adenylic and guanylic nucleotides have specific roles. For example, GTP is critical for translation and for signaling through GTPases, while ATP is the major energyproviding molecule in the cell. In yeast, intracellular concentrations of ATP and GTP are clearly different ($5 and 1.5 mm, respectively; Breton et al. 2008;Gauthier et al. 2008), most probably as the result of regulatory processes that maintain homeostasis. In most eukaryotic cells, including yeast, adenylic and guanylic nucleotides either are synthesized from a common precursor (IMP) or are recycled from preformed bases or nucleosides (Figure 1). While most enzymes involved in these processes have been identified, the physiological consequences of purine nucleotide imbalance are far from being understood. Interestingly, drugs specifically inhibiting GTP synthesis, such as mycophenolic acid (MPA), have a strong immunosuppressive effect and are now widely used to limit allograft rejection. We have previously established the effect of MPA on the yeast proteome and have identified numerous yeast mutants hypersensitive to this drug (Desmoucelles et al. 2002). MPA effects are due to GTP shortage, since they are reversed by exogenous guanine, allowing replenishment of the GTP pool. However, drugs often have secondary effects and can be detoxified and/or diluted during cell growth. As an alternative, consequences of purine nucleotide imbalance can be investigated using yeast mutants. In two previous studies, we have used specific mutants to increase the GTP pool or decrease the ATP pool (Breton et al. 2008;Gauthier et al. 20...

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Revisiting Purine-Histidine Cross-Pathway Regulation in Saccharomyces cerevisiae

Cited by 89 publications

References 39 publications

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Novel Acid Phosphatase in Candida glabrata Suggests Selective Pressure and Niche Specialization in the Phosphate Signal Transduction Pathway

Phenotypic Consequences of Purine Nucleotide Imbalance inSaccharomyces cerevisiae

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