scholarly journals Integration of Transcriptional and Posttranslational Regulation in a Glucose Signal Transduction Pathway in Saccharomyces cerevisiae

2006 ◽  
Vol 5 (1) ◽  
pp. 167-173 ◽  
Author(s):  
Jeong-Ho Kim ◽  
Valérie Brachet ◽  
Hisao Moriya ◽  
Mark Johnston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Glucose Repression ◽  
Signal Transduction Pathway ◽  
Feedback Regulation ◽  
Glucose Sensing ◽  
26S Proteasome ◽  
Posttranslational Regulation ◽  
Glucose Signaling ◽  
Genes Encoding ◽  
Glucose Induction

ABSTRACT Expression of the HXT genes encoding glucose transporters in the budding yeast Saccharomyces cerevisiae is regulated by two interconnected glucose-signaling pathways: the Snf3/Rgt2-Rgt1 glucose induction pathway and the Snf1-Mig1 glucose repression pathway. The Snf3 and Rgt2 glucose sensors in the membrane generate a signal in the presence of glucose that inhibits the functions of Std1 and Mth1, paralogous proteins that regulate the function of the Rgt1 transcription factor, which binds to the HXT promoters. It is well established that glucose induces degradation of Mth1, but the fate of its paralogue Std1 has been less clear. We present evidence that glucose-induced degradation of Std1 via the SCFGrr1 ubiquitin-protein ligase and the 26S proteasome is obscured by feedback regulation of STD1 expression. Disappearance of Std1 in response to glucose is accelerated when glucose induction of STD1 expression due to feedback regulation by Rgt1 is prevented. The consequence of relieving feedback regulation of STD1 expression is that reestablishment of repression of HXT1 expression upon removal of glucose is delayed. In contrast, degradation of Mth1 is reinforced by glucose repression of MTH1 expression: disappearance of Mth1 is slowed when glucose repression of MTH1 expression is prevented, and this results in a delay in induction of HXT3 expression in response to glucose. Thus, the cellular levels of Std1 and Mth1, and, as a consequence, the kinetics of induction and repression of HXT gene expression, are closely regulated by interwoven transcriptional and posttranslational controls mediated by two different glucose-sensing pathways.

scholarly journals Regulatory Network Connecting Two Glucose Signal Transduction Pathways in Saccharomyces cerevisiae

2004 ◽  
Vol 3 (1) ◽  
pp. 221-231 ◽  
Author(s):  
Aneta Kaniak ◽  
Zhixiong Xue ◽  
Daniel Macool ◽  
Jeong-Ho Kim ◽  
Mark Johnston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Transcription Factor ◽  
Regulatory Network ◽  
Target Genes ◽  
Glucose Repression ◽  
Signal Transduction Pathways ◽  
Glucose Signaling ◽  
Genes Encoding ◽  
Glucose Induction

ABSTRACT The yeast Saccharomyces cerevisiae senses glucose, its preferred carbon source, through multiple signal transduction pathways. In one pathway, glucose represses the expression of many genes through the Mig1 transcriptional repressor, which is regulated by the Snf1 protein kinase. In another pathway, glucose induces the expression of HXT genes encoding glucose transporters through two glucose sensors on the cell surface that generate an intracellular signal that affects function of the Rgt1 transcription factor. We profiled the yeast transcriptome to determine the range of genes targeted by this second pathway. Candidate target genes were verified by testing for Rgt1 binding to their promoters by chromatin immunoprecipitation and by measuring the regulation of the expression of promoter lacZ fusions. Relatively few genes could be validated as targets of this pathway, suggesting that this pathway is primarily dedicated to regulating the expression of HXT genes. Among the genes regulated by this glucose signaling pathway are several genes involved in the glucose induction and glucose repression pathways. The Snf3/Rgt2-Rgt1 glucose induction pathway contributes to glucose repression by inducing the transcription of MIG2, which encodes a repressor of glucose-repressed genes, and regulates itself by inducing the expression of STD1, which encodes a regulator of the Rgt1 transcription factor. The Snf1-Mig1 glucose repression pathway contributes to glucose induction by repressing the expression of SNF3 and MTH1, which encodes another regulator of Rgt1, and also regulates itself by repressing the transcription of MIG1. Thus, these two glucose signaling pathways are intertwined in a regulatory network that serves to integrate the different glucose signals operating in these two pathways.

Glucose as a hormone: receptor-mediated glucose sensing in the yeast Saccharomyces cerevisiae

2005 ◽  
Vol 33 (1) ◽  
pp. 247-252 ◽  
Author(s):  
M. Johnston ◽  
J.-H. Kim
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Glucose Transporters ◽  
Glucose Sensing ◽  
Yeast Cells ◽  
Transduction Pathway ◽  
Yeast Saccharomyces Cerevisiae ◽  
Expression Of Genes ◽  
Genes Encoding

Because glucose is the principal carbon and energy source for most cells, most organisms have evolved numerous and sophisticated mechanisms for sensing glucose and responding to it appropriately. This is especially apparent in the yeast Saccharomyces cerevisiae, where these regulatory mechanisms determine the distinctive fermentative metabolism of yeast, a lifestyle it shares with many kinds of tumour cells. Because energy generation by fermentation of glucose is inefficient, yeast cells must vigorously metabolize glucose. They do this, in part, by carefully regulating the first, rate-limiting step of glucose utilization: its transport. Yeast cells have learned how to sense the amount of glucose that is available and respond by expressing the most appropriate of its 17 glucose transporters. They do this through a signal transduction pathway that begins at the cell surface with the Snf3 and Rgt2 glucose sensors and ends in the nucleus with the Rgt1 transcription factor that regulates expression of genes encoding glucose transporters. We explain this glucose signal transduction pathway, and describe how it fits into a highly interconnected regulatory network of glucose sensing pathways that probably evolved to ensure rapid and sensitive response of the cell to changing levels of glucose.

scholarly journals Glucose Regulation of Saccharomyces cerevisiae Cell Cycle Genes

2003 ◽  
Vol 2 (1) ◽  
pp. 143-149 ◽  
Author(s):  
Laura L. Newcomb ◽  
Jasper A. Diderich ◽  
Matthew G. Slattery ◽  
Warren Heideman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Glucose Repression ◽  
Nutrient Sensing ◽  
Glucose Response ◽  
Glucose Signaling ◽  
Expression Of Genes ◽  
Proliferative Growth ◽  
Cell Cycle Regulatory Proteins ◽  
Glucose Induction

ABSTRACT Nutrient-limited Saccharomyces cerevisiae cells rapidly resume proliferative growth when transferred into glucose medium. This is preceded by a rapid increase in CLN3, BCK2, and CDC28 mRNAs encoding cell cycle regulatory proteins that promote progress through Start. We have tested the ability of mutations in known glucose signaling pathways to block glucose induction of CLN3, BCK2, and CDC28. We find that loss of the Snf3 and Rgt2 glucose sensors does not block glucose induction, nor does deletion of HXK2, encoding the hexokinase isoenzyme involved in glucose repression signaling. Rapamycin blockade of the Tor nutrient sensing pathway does not block the glucose response. Addition of 2-deoxy glucose to the medium will not substitute for glucose. These results indicate that glucose metabolism generates the signal required for induction of CLN3, BCK2, and CDC28. In support of this conclusion, we find that addition of iodoacetate, an inhibitor of the glyceraldehyde-3-phosphate dehydrogenase step in yeast glycolysis, strongly downregulates the levels CLN3, BCK2, and CDC28 mRNAs. Furthermore, mutations in PFK1 and PFK2, which encode phosphofructokinase isoforms, inhibit glucose induction of CLN3, BCK2, and CDC28. These results indicate a link between the rate of glycolysis and the expression of genes that are critical for passage through G1.

scholarly journals Rgt1, a glucose sensing transcription factor, is required for transcriptional repression of the HXK2 gene in Saccharomyces cerevisiae

2005 ◽  
Vol 388 (2) ◽  
pp. 697-703 ◽  
Author(s):  
Aaron PALOMINO ◽  
Pilar HERRERO ◽  
Fernando MORENO
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Transcriptional Repression ◽  
Glucose Repression ◽  
Fold Increase ◽  
Glucose Sensing ◽  
Start Codon ◽  
Dependent Manner ◽  
Gene Encoding ◽  
Regulatory Functions

Expression of HXK2, a gene encoding a Saccharomyces cerevisiae bifunctional protein with catalytic and regulatory functions, is controlled by glucose availability, being activated in the presence of glucose and inhibited when the levels of the sugar are low. In the present study, we identified Rgt1 as a transcription factor that, together with the Med8 protein, is essential for repression of the HXK2 gene in the absence of glucose. Rgt1 represses HXK2 expression by binding specifically to the motif (CGGAAAA) located at −395 bp relative to the ATG translation start codon in the HXK2 promoter. Disruption of the RGT1 gene causes an 18-fold increase in the level of HXK2 transcript in the absence of glucose. Rgt1 binds to the RGT1 element of HXK2 promoter in a glucose-dependent manner, and the repression of target gene depends on binding of Rgt1 to DNA. The physiological significance of the connection between two glucose-signalling pathways, the Snf3/Rgt2 that causes glucose induction and the Mig1/Hxk2 that causes glucose repression, was also analysed.

The Saccharomyces cerevisiae ADR1 gene is a positive regulator of transcription of genes encoding peroxisomal proteins

1991 ◽  
Vol 11 (2) ◽  
pp. 699-704 ◽  
Author(s):  
M Simon ◽  
G Adam ◽  
W Rapatz ◽  
W Spevak ◽  
H Ruis
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Glucose Repression ◽  
Northern Hybridization ◽  
Multicopy Plasmid ◽  
Beta Oxidation ◽  
Positive Regulator ◽  
Ethanol Medium ◽  
Genes Encoding ◽  
Multiple Copies ◽  
Regulatory Functions

Expression of the CTA1 gene of Saccharomyces cerevisiae, encoding catalase A, the peroxisomal catalase of this yeast, is sensitive to glucose repression. A DNA fragment cloned as a multicopy plasmid suppressing the glucose repression of CTA1 transcription was demonstrated to contain the ADR1 gene. Multiple copies of ADR1 increased catalase A formation not only on 10% glucose, but also on ethanol medium and in the presence of oleic acid, an inducer of peroxisome proliferation. Compared with wild-type cells, adr1 null mutants produced by disruption of the gene exhibit reduced CTA1 expression. This demonstrates that ADR1 is a true positive regulator of CTA1. Further experiments showed that it acts directly on CTA1. Alcohol dehydrogenase II, which is under ADR1 control, was excluded as a mediator of the effect on CTA1; deletion of bases -123 to -168 of CTA1 reduces expression and eliminates the response to the ADR1 multicopy plasmid without eliminating fatty acid induction; and gel retardation experiments demonstrated that ADR1 binds to a CTA1 upstream fragment (-156 to -184) with limited similarity to the ADR1 binding site of ADH2. Northern hybridization experiments further demonstrated that expression of two genes encoding enzymes of peroxisomal beta-oxidation (beta-ketothiolase, trifunctional enzyme) and of a gene involved in peroxisome assembly (PAS1) is also negatively affected by the adr1 null mutation. These findings demonstrate that the ADR1 protein has much broader regulatory functions than previously recognized.

scholarly journals A novel signal transduction pathway in Saccharomyces cerevisiae defined by Snf3-regulated expression of HXT6.

1996 ◽  
Vol 7 (12) ◽  
pp. 1953-1966 ◽  
Author(s):  
H Liang ◽  
R F Gaber
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Glucose Uptake ◽  
Glucose Repression ◽  
Carbon Sources ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Signaling Mechanism ◽  
High Concentrations ◽  
Delta Cells

We show that cells deleted for SNF3, HXT1, HXT2, HXT3, HXT4, HXT6, and HXT7 do not take up glucose and cannot grow on media containing glucose as a sole carbon source. The expression of Hxt1, Hxt2, Hxt3, Hxt6, or Gal2 in these cells resulted in glucose transport and allowed growth on glucose media. In contrast, the expression of Snf3 failed to confer glucose uptake or growth on glucose. HXT6 is highly expressed on raffinose, low glucose, or nonfermentable carbon sources but is repressed in the presence of high concentrations of glucose. The maintenance of HXT6 glucose repression is strictly dependent on Snf3 and not on intracellular glucose. In snf3 delta cells expression of HXT6 is constitutive even when the entire repertoire of HXT genes is present and glucose uptake is abundant. In addition, glucose repression of HXT6 does not require glucose uptake by HXT1, HXT2, HXT3 or HXT4. We show that a signal transduction pathway defined by the Snf3-dependent hexose regulation of HXT6 is distinct from but also overlaps with general glucose regulation pathways in Saccharomyces cerevisiae. Finally, glucose repression of ADH2 and SUC2 is intact in snf3 delta hxt1 delta hxt2 delta hxt3 delta hxt4 delta hxt6 delta hxt7 delta gal2 cells, suggesting that the sensing and signaling mechanism for general glucose repression is independent from glucose uptake.

Altered regulatory responses to glucose are associated with a glucose transport defect in grr1 mutants of Saccharomyces cerevisiae.

Genetics ◽  
1994 ◽  
Vol 136 (4) ◽  
pp. 1279-1285 ◽  
Author(s):  
L G Vallier ◽  
D Coons ◽  
L F Bisson ◽  
M Carlson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Glucose Transport ◽  
Divalent Cation ◽  
Glucose Transporter ◽  
Glucose Repression ◽  
Cation Transport ◽  
Glucose Sensing ◽  
Transporter Gene ◽  
High Affinity ◽  
Transport Defect

Abstract The GRR1 gene of Saccharomyces cerevisiae affects glucose repression, cell morphology, divalent cation transport and other processes. We present a kinetic analysis showing that the grr1 mutant is also defective in high affinity glucose transport. In combination with a mutation in SNF3, a member of the glucose transporter gene family, grr1 strikingly impairs growth on glucose. These findings suggest that GRR1 and SNF3 affect glucose transport by distinct pathways. The mutation rgt1-1, a suppressor of snf3, restores both glucose transport and glucose repression to a grr1 mutant, but does not remedy the morphological defect. We suggest that GRR1 affects the glucose sensing process and that the association between transport and regulation may reflect the involvement of a transporter in glucose sensing.

scholarly journals The Saccharomyces cerevisiae ADR1 gene is a positive regulator of transcription of genes encoding peroxisomal proteins.

1991 ◽  
Vol 11 (2) ◽  
pp. 699-704 ◽  
Author(s):  
M Simon ◽  
G Adam ◽  
W Rapatz ◽  
W Spevak ◽  
H Ruis
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Glucose Repression ◽  
Northern Hybridization ◽  
Multicopy Plasmid ◽  
Beta Oxidation ◽  
Positive Regulator ◽  
Ethanol Medium ◽  
Genes Encoding ◽  
Multiple Copies ◽  
Regulatory Functions

Expression of the CTA1 gene of Saccharomyces cerevisiae, encoding catalase A, the peroxisomal catalase of this yeast, is sensitive to glucose repression. A DNA fragment cloned as a multicopy plasmid suppressing the glucose repression of CTA1 transcription was demonstrated to contain the ADR1 gene. Multiple copies of ADR1 increased catalase A formation not only on 10% glucose, but also on ethanol medium and in the presence of oleic acid, an inducer of peroxisome proliferation. Compared with wild-type cells, adr1 null mutants produced by disruption of the gene exhibit reduced CTA1 expression. This demonstrates that ADR1 is a true positive regulator of CTA1. Further experiments showed that it acts directly on CTA1. Alcohol dehydrogenase II, which is under ADR1 control, was excluded as a mediator of the effect on CTA1; deletion of bases -123 to -168 of CTA1 reduces expression and eliminates the response to the ADR1 multicopy plasmid without eliminating fatty acid induction; and gel retardation experiments demonstrated that ADR1 binds to a CTA1 upstream fragment (-156 to -184) with limited similarity to the ADR1 binding site of ADH2. Northern hybridization experiments further demonstrated that expression of two genes encoding enzymes of peroxisomal beta-oxidation (beta-ketothiolase, trifunctional enzyme) and of a gene involved in peroxisome assembly (PAS1) is also negatively affected by the adr1 null mutation. These findings demonstrate that the ADR1 protein has much broader regulatory functions than previously recognized.

Mutations in GSF1 and GSF2 Alter Glucose Signaling in Saccharomyces cerevisiae

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 557-566 ◽  
Author(s):  
Peter W Sherwood ◽  
Marian Carlson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Slow Growth ◽  
Glucose Repression ◽  
Snf1 Kinase ◽  
Glucose Signaling ◽  
Glucose Depletion ◽  
Complementation Groups ◽  
Growth Phenotype ◽  
His3 Gene ◽  
Slow Growth Phenotype

One function of the Saccharomyces cerevisiae Snf1 protein kinase is to relieve glucose repression of SUC, GAL, and other genes in response to glucose depletion. To identify genes that regulate Snf1 kinase activity, we have selected mutants that inappropriately express a SUC2promoter::HIS3 gene fusion when grown in glucose and that require Snf1 function for this phenotype. Mutations representing two new complementation groups (gsf1 and gsf2) were isolated. gsf1 mutations affect two distinct responses to glucose: the Snf1-regulated glucose repression of SUC2 and GAL10 transcription and the Snf1-independent induction by glucose of HXT1 transcription. gsf2 mutations relieve glucose repression of SUC2 and GAL10 transcription and, in combination with snf1Δ, cause an extreme slow growth phenotype. The GSF2 gene was cloned by complementation of the gsf2-1 snf1Δ slow growth phenotype and encodes a previously uncharacterized 46 kD protein.

scholarly journals Regulatory Mechanisms Controlling Expression of the DAN/TIR Mannoprotein Genes During Anaerobic Remodeling of the Cell Wall in Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1169-1177
Author(s):  
Natalia E Abramova ◽  
Brian D Cohen ◽  
Odeniel Sertil ◽  
Rachna Kapoor ◽  
Kelvin J A Davies ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Consensus Sequence ◽  
Ectopic Expression ◽  
Constitutive Expression ◽  
Anaerobic Growth ◽  
Zinc Cluster ◽  
Sterol Transport ◽  
Genes Encoding ◽  
Altered Regulation ◽  
Repression Domain

Abstract The DAN/TIR genes of Saccharomyces cerevisiae encode homologous mannoproteins, some of which are essential for anaerobic growth. Expression of these genes is induced during anaerobiosis and in some cases during cold shock. We show that several heme-responsive mechanisms combine to regulate DAN/TIR gene expression. The first mechanism employs two repression factors, Mox1 and Mox2, and an activation factor, Mox4 (for mannoprotein regulation by oxygen). The genes encoding these proteins were identified by selecting for recessive mutants with altered regulation of a dan1::ura3 fusion. MOX4 is identical to UPC2, encoding a binucleate zinc cluster protein controlling expression of an anaerobic sterol transport system. Mox4/Upc2 is required for expression of all the DAN/TIR genes. It appears to act through a consensus sequence termed the AR1 site, as does Mox2. The noninducible mox4Δ allele was epistatic to the constitutive mox1 and mox2 mutations, suggesting that Mox1 and Mox2 modulate activation by Mox4 in a heme-dependent fashion. Mutations in a putative repression domain in Mox4 caused constitutive expression of the DAN/TIR genes, indicating a role for this domain in heme repression. MOX4 expression is induced both in anaerobic and cold-shocked cells, so heme may also regulate DAN/TIR expression through inhibition of expression of MOX4. Indeed, ectopic expression of MOX4 in aerobic cells resulted in partially constitutive expression of DAN1. Heme also regulates expression of some of the DAN/TIR genes through the Rox7 repressor, which also controls expression of the hypoxic gene ANB1. In addition Rox1, another heme-responsive repressor, and the global repressors Tup1 and Ssn6 are also required for full aerobic repression of these genes.

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