The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione s-transferases.

Coschigano, Peter W.; Magasanik, Boris

doi:10.1128/mcb.11.2.822

Cited by 258 publications

(218 citation statements)

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“…Mutations in the URE2IGDHCR gene (Grenson, 1969;Drillien and Lacroute, 1972;Grenson et a/., 1974) at least partially relieve nitrogen repression of Gln3p (Courchesne and Magasanik, 1988). The Ure2/GdhCR protein is somewhat similar to glutathione transferases (Coschigano and Magasanik, 1991) and has the peculiar ability to generate prion analogues (Wickner, 1994). Although Ure2p was recently reported to bind to Gln3p (Blinder et a/., 1996), exactly how it negatively controls Gln3p remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Gzf3p, a fourth GATA factor involved in nitrogen‐regulated transcription in Saccharomyces cerevisiae

Soussi‐Boudekou

Vissers

Urrestarazu

et al. 1997

Molecular Microbiology

101

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Summary In Saccharomyces cerevisiae, two positive transcription factors of the GATA family, Gln3p and NiMp/ Gatlp, upregulate the expression of multiple nitrogen pathway genes via upstream 5‐GATA‐3′ sequences. Another GATA factor, Uga43p/Da180p, downregulates to varying degrees the expression of some nitrogen‐regulated genes. Here, we report the functional analysis of a fourth GATA factor, Gzf 3p/Ni12p, whose gene was discovered by systematic sequencing of chromosome X. The Gzf3 protein most closely resembles Uga43p. Similar to Uga43p, Gzf3p has the properties of a negative GATA factor. While Uga43p is active specifically under nitrogen‐derepression conditions, Gzf 3p exerts its negative regulatory function specifically on preferred nitrogen sources: it is involved in nitrogen repression of NiMp‐dependent transcription. At least one positive GATA factor is required for the UGA43 and GZF3 genes to be expressed. The Uga43p factor negatively regulates GZF3 expression and vice versa. In addition, both Uga43p and Gzf3p moderately regulate expression of their own genes. These two proteins seem to be parts of a complex network of GATA factors which probably play a determining role in nitrogen‐regulated transcription.

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Section: Introductionmentioning

confidence: 99%

Gzf3p, a fourth GATA factor involved in nitrogen‐regulated transcription in Saccharomyces cerevisiae

Soussi‐Boudekou

Vissers

Urrestarazu

et al. 1997

Molecular Microbiology

101

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“…A connection between the retrograde pathway and nitrogen metabolism has recently been uncovered by the finding that the target of rapamycin (TOR) kinase pathway in yeast also involves the RTG genes (Komeili et al, 2000;Shamji et al, 2000). The TOR kinase pathway promotes the formation of a complex between Gln3p, a transcription factor that controls the expression of genes required for the utilization of poor nitrogen sources (Mitchell and Magasanik, 1984;Courchesne and Magasanik, 1988;Coschigano and Magasanik, 1991;Blinder et al, 1996), and Ure2p, a negative regulator of Gln3p (Beck and Hall, 1999). When the TOR kinase pathway is inhibited by rapamycin, or when cells are grown on a poor nitrogen source such as urea, Rtg1p and Rtg3p translocate from the cytoplasm to the nucleus in an Rtg2p-dependent manner to activate target gene expression (Komeili et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

RTG-dependent Mitochondria-to-Nucleus Signaling Is Regulated by MKS1 and Is Linked to Formation of Yeast Prion [URE3]

Sekito¹

2002

Molecular Biology of the Cell

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An important function of the RTG signaling pathway is maintenance of intracellular glutamate supplies in yeast cells with dysfunctional mitochondria. Herein, we report that MKS1 is a negative regulator of the RTG pathway, acting between Rtg2p, a proximal sensor of mitochondrial function, and the bHLH transcription factors Rtg1p and Rtg3p. In mks1⌬ cells, RTG target gene expression is constitutive, bypassing the requirement for Rtg2p, and is no longer repressible by glutamate. We show further that Mks1p is a phosphoprotein whose phosphorylation pattern parallels that of Rtg3p in response to activation of the RTG pathway, and that Mks1p is in a complex with Rtg2p. MKS1 was previously implicated in the formation of [URE3], an inactive prion form of a negative regulator of the nitrogen catabolite repression pathway, Ure2p. rtg⌬ mutations induce [URE3] and can do so independently of MKS1. We find that glutamate suppresses [URE3] formation, suggesting that the Mks1p effect on the formation of [URE3] can occur indirectly via regulation of the RTG pathway. INTRODUCTIONCells are able to monitor and respond to the functional state of their organelles. In animal cells, for example, compromises in mitochondrial function or certain external cues can lead to increased expression of genes encoding components of the mitochondrial oxidative phosphorylation apparatus and, in some instances, lead to a general increase in the biogenesis of mitochondria (Lunardi and Attardi, 1991;Scarpulla, 1997;Biswas et al., 1999;Heddi et al., 1999;Murdock et al., 1999;Wu et al., 1999;Amuthan et al., 2001). These events are controlled, in part, by transcriptional activators and coactivators whose targets include nuclear genes encoding mitochondrial proteins.Yeast cells also respond to mitochondrial dysfunction by altering the expression of a subset of nuclear genes (Parikh et al., 1987(Parikh et al., , 1989. This response, called retrograde regulation, functions to better adapt cells to the mitochondrial defects. In derepressed, respiratory-deficient cells, such as those that have lost their mitochondrial DNA ( petites), the expression of genes involved in anaplerotic pathways, small molecule transport, peroxisomal activities, and stress responses is up-regulated (Liao et al., 1991;Liu and Butow, 1999;Hallstrom and Moye-Rowley, 2000;Traven et al., 2000;Epstein et al., 2001). In many cases, these changes in gene expression reflect activities that would compensate for the block in the tricarboxylic acid (TCA) cycle caused by the respiratory defect. Expression of a number of these retrograde responsive genes, such as CIT2, DLD3, and PDH1 encoding, respectively, a glyoxylate cycle isoform of citrate synthase, a cytosolic d-lactate dehydrogenase, and a protein involved in propionate metabolism, is controlled by RTG1, RTG2, and RTG3. Rtg1p and Rtg3p are basic helix-loop-helix transcription factors (Jia et al., 1997), and Rtg2p is a cytoplasmic protein with an N-terminal ATP-binding domain similar to that of the actin/sugar kinase/hsp70 superfamily (Bork...

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“…The Ure2 system is therefore a useful model not only to investigate the prion concept, but also to understand the properties of Gln/ Asn-repeat proteins and hence the molecular basis of the related diseases. [27,29,58], Sup35 [114,115], Rnq1 [13], Het-s [22] and PrP [23,24,116,117]. The functional regions are as indicated.…”

Section: Introductionmentioning

confidence: 99%

“…The C-terminal region of Ure2 shows structural similarity to glutathione transferases (GSTs) and is necessary and sufficient for its regulatory function: Ure2 interacts with the transcription factor Gln3 allowing control of nitrogen catabolite repression, blocking the uptake of poor nitrogen sources in the presence of a good nitrogen source [29,30]. The N-terminal region of Ure2 is required for its prion properties in vivo [31] and to form amyloid-like filaments in vitro [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

The yeast prion protein Ure2: Structure, function and folding

Lian

Jiang

Zhang

et al. 2006

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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The Saccharomyces cerevisiae protein Ure2 functions as a regulator of nitrogen metabolism and as a glutathione-dependent peroxidase. Ure2 also has the characteristics of a prion, in that it can undergo a heritable conformational change to an aggregated state; the prion form of Ure2 loses the regulatory function, but the enzymatic function appears to be maintained. A number of factors are found to affect the prion properties of Ure2, including mutation and expression levels of molecular chaperones, and the effect of these factors on structure and stability are being investigated. The relationship between structure, function and folding for the yeast prion Ure2 are discussed.

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The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione s-transferases.

Cited by 258 publications

References 53 publications

Gzf3p, a fourth GATA factor involved in nitrogen‐regulated transcription in Saccharomyces cerevisiae

Gzf3p, a fourth GATA factor involved in nitrogen‐regulated transcription in Saccharomyces cerevisiae

RTG-dependent Mitochondria-to-Nucleus Signaling Is Regulated by MKS1 and Is Linked to Formation of Yeast Prion [URE3]

The yeast prion protein Ure2: Structure, function and folding

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