Glucose repression may involve processes with different sugar kinase requirements

Sanz, Pascual; Nieto, Almudena; Prieto, José A.

doi:10.1128/jb.178.15.4721-4723.1996

Cited by 31 publications

(30 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…(iii) Mutant alleles with low catalytic activity were still fully functional in glucose signaling (32). In this context it is also interesting to point out that early glucose repression of the SUC2 gene does not specifically require Hxk2 (33) and that Hxk2 is only necessary for the long term glucose response (34). Thus, the correlation between glucose phosphorylation activity of Hxk2 and glucose repression appears less likely at present.…”

Section: Discussionmentioning

confidence: 97%

The Glucose-regulated Nuclear Localization of Hexokinase 2 in Saccharomyces cerevisiae Is Mig1-dependent

Ahuatzi¹,

Herrero²,

la³

et al. 2004

Journal of Biological Chemistry

116

186

View full text Add to dashboard Cite

Two major mediators of glucose repression in Saccharomyces cerevisiae are the proteins Mig1 and Hxk2. The mechanism of Hxk2-dependent glucose repression pathway is not well understood, but the Mig1-dependent part of the pathway has been elucidated in great detail. Here we report that Hxk2 has a glucose-regulated nuclear localization and that Mig1, a transcriptional repressor responsible for glucose repression of many genes, is required to sequester Hxk2 into the nucleus. Mig1 and Hxk2 interacted in vivo in a yeast two-hybrid assay and in vitro in immunoprecipitation and glutathione S-transferase pull-down experiments. We found that the Lys 6 -Met 15 decapeptide of Hxk2, which is necessary for nuclear localization of the protein, is also essential for interaction with the Mig1 protein. Our results also show that the Hxk2-Mig1 interaction is of physiological significance because both proteins have been found interacting together in a cluster with DNA fragments containing the MIG1 site of SUC2 promoter. We conclude that Hxk2 operates by interacting with Mig1 to generate a repressor complex located in the nucleus of S. cerevisiae during growth in glucose medium.The yeast Saccharomyces cerevisiae can use different carbon sources for growth, but evolution has selected mechanisms for the preferential and efficient utilization of glucose. In this yeast, glucose regulates carbon utilization mainly by the repression or activation of the transcription of numerous genes that encode enzymes implicated in carbon metabolism (1, 2). Although several of the genes implicated in the pathways that control glucose repression have been identified, a complete mechanistic picture of the process is not yet available. The Hxk2 and Mig1 proteins participate as important repressors in the glucose signaling pathway (3, 4).Hxk2 is the protein that initiates the intracellular metabolism of glucose by its phosphorylation at C-6, but in addition it plays a vital role in glucose repression (5). In hxk2 mutants repression of several genes by glucose is no longer operative (6, 7). If Hxk2 acts as a transcriptional repressor, it should be found in the cell nucleus at least under certain conditions. In fact, results obtained using different approaches have demonstrated that about 15% of the protein is localized in the nucleus (8,9) and that this localization is required for glucose repression of SUC2, HXK1, and GLK1 genes (9, 10). Moreover it has been shown that the nuclear Hxk2 is involved in the formation of specific DNA-protein complexes during glucose-dependent repression of these genes (9, 10).Mig1 is a C 2 H 2 zinc finger protein that binds to the motif WWWWWN(G/C)(C/T)GGGG in several promoters (11). Once bound to this MIG1 element, it recruits the Tup1-Cyc8 (Ssn6p) complex that represses gene transcription during growth in glucose (12). The activity of Mig1 is regulated by phosphorylation and subcellular localization. In high glucose, Mig1 is dephosphorylated by the Glc7-Reg1 protein phosphatase complex (13) and is located in the nucleus wher...

show abstract

Section: Discussionmentioning

confidence: 97%

The Glucose-regulated Nuclear Localization of Hexokinase 2 in Saccharomyces cerevisiae Is Mig1-dependent

Ahuatzi¹,

Herrero²,

la³

et al. 2004

Journal of Biological Chemistry

116

186

View full text Add to dashboard Cite

show abstract

“…Indeed, glucose induction of MIG2 expression is sufficient to account for the glucose activation of Mig2 function ( Table 9). The two main glucose repressors, Mig1 and Mig2, are mostly redundant (43,66) but are regulated in different ways by different signaling pathways responding to different glucose signals, one of which operates through Snf1, is dependent on the Glc7 phosphatase and hexokinase (58,64), and is probably based on glucose metabolism and the other of which operates through the glucose sensors to sense extracellular glucose by receptor-mediated signaling. Thus, the phenomenon of the glucose repression of gene expression is a result of outputs from two glucose signal transduction pathways: the Mig1 component regulated by the Snf1 kinase and the Mig2 (and the ancillary Mig3) component regulated at the level of their transcription by the Snf3/Rgt2-Rgt1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Regulatory Network Connecting Two Glucose Signal Transduction Pathways in Saccharomyces cerevisiae

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

“…Although Hxk2 is required for glucose repression of many genes, phosphorylation of glucose by any of the three glucose kinases Hxk1, Hxk2, or Glk1 is sufficient to trigger some glucose repression mechanisms (De Winde et al 1996;Sanz et al 1996;Yin et al 1996). To test whether glucose phosphorylation is required for the glucose-dependent nuclear exclusion of Gal83, we examined hxk1⌬ hxk2⌬ and hxk1⌬ hxk2⌬ glk1⌬ mutants.…”

Section: Nuclear Exclusion Of Gal83 In Glucose-grown Cells Depends Onmentioning

confidence: 99%

Subcellular localization of the Snf1 kinase is regulated by specific β subunits and a novel glucose signaling mechanism

Vincent¹,

Townley²,

Kuchin³

et al. 2001

Genes Dev.

244

323

View full text Add to dashboard Cite

The Snf1/AMP-activated protein kinase family has broad roles in transcriptional, metabolic, and developmental regulation in response to stress. In Saccharomyces cerevisiae, Snf1 is required for the response to glucose limitation. Snf1 kinase complexes contain the ␣ (catalytic) subunit Snf1, one of the three related ␤ subunits Gal83, Sip1, or Sip2, and the ␥ subunit Snf4. We present evidence that the ␤ subunits regulate the subcellular localization of the Snf1 kinase. Green fluorescent protein fusions to Gal83, Sip1, and Sip2 show different patterns of localization to the nucleus, vacuole, and/or cytoplasm. We show that Gal83 directs Snf1 to the nucleus in a glucose-regulated manner. We further identify a novel signaling pathway that controls this nuclear localization in response to glucose phosphorylation. This pathway is distinct from the glucose signaling pathway that inhibits Snf1 kinase activity and responds not only to glucose but also to galactose and sucrose. Such independent regulation of the localization and the activity of the Snf1 kinase, combined with the distinct localization of kinases containing different ␤ subunits, affords versatility in regulating physiological responses.

show abstract

Glucose repression may involve processes with different sugar kinase requirements

Cited by 31 publications

References 21 publications

The Glucose-regulated Nuclear Localization of Hexokinase 2 in Saccharomyces cerevisiae Is Mig1-dependent

The Glucose-regulated Nuclear Localization of Hexokinase 2 in Saccharomyces cerevisiae Is Mig1-dependent

Regulatory Network Connecting Two Glucose Signal Transduction Pathways in Saccharomyces cerevisiae

Subcellular localization of the Snf1 kinase is regulated by specific β subunits and a novel glucose signaling mechanism

Contact Info

Product

Resources

About