Adr1 and Cat8 synergistically activate the glucose-regulated alcohol dehydrogenase gene ADH2 of the yeast Saccharomyces cerevisiae

Walther, Kristin; Schüller, Hans‐Joachim

doi:10.1099/00221287-147-8-2037

Cited by 55 publications

(49 citation statements)

References 45 publications

(47 reference statements)

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“…For Cat8, in vitro binding has been demonstrated by electrophoretic mobility shift assays to the CSRE (carbon source-responsive element) sequences from ACS1, ADH2, ICL2, ICL1, FBP1, MDH2, MLS1, and PCK1 (9,28,35,36,39,47,51). All of these genes are known to be regulated by Cat8 under derepressing conditions.…”

Section: Resultsmentioning

confidence: 99%

Combined Global Localization Analysis and Transcriptome Data Identify Genes That Are Directly Coregulated by Adr1 and Cat8

Tachibana

Yoo

Tagne

et al. 2005

Molecular and Cellular Biology

141

164

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In Saccharomyces cerevisiae, glucose depletion causes a profound alteration in metabolism, mediated in part by global transcriptional changes. Many of the transcription factors that regulate these changes act combinatorially. We have analyzed combinatorial regulation by Adr1 and Cat8, two transcription factors that act during glucose depletion, by combining genome-wide expression and genome-wide binding data. We identified 32 genes that are directly activated by Adr1, 28 genes that are directly activated by Cat8, and 14 genes that are directly regulated by both. Our analysis also uncovered promoters that Adr1 binds but does not regulate and promoters that are indirectly regulated by Cat8, stressing the advantage of combining global expression and global localization analysis to find directly regulated targets. At most of the coregulated promoters, the in vivo binding of one factor is independent of the other, but Adr1 is required for optimal Cat8 binding at two promoters with a poor match to the Cat8 binding consensus. In addition, Cat8 is required for Adr1 binding at promoters where Adr1 is not required for transcription. These data provide a comprehensive analysis of the direct, indirect, and combinatorial requirements for these two global transcription factors.Cells respond to stresses such as variations in temperature, pH or osmotic or nutrient conditions by altering the expression of genes that allow the cell to respond to the new environment (10). These transcriptional changes are initiated by signals that converge on a limited number of transcription factors, which then act combinatorially to control many genes in multiple pathways. Microarrays can be used to identify these coordinated, combinatorial responses by detecting both the localization of key transcription factors and the corresponding changes in the transcriptome (1).

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Section: Resultsmentioning

confidence: 99%

Combined Global Localization Analysis and Transcriptome Data Identify Genes That Are Directly Coregulated by Adr1 and Cat8

Tachibana

Yoo

Tagne

et al. 2005

Molecular and Cellular Biology

141

164

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“…For example, two genes involved in ethanol metabolism, ADH2 and ACS1, are co-regulated by Adr1 and Cat8 in a synergistic manner (22). The genes of ␤-oxidation that are ADR1-dependent are also regulated by oleate induction through the transcription factor Oaf1⅐Pip2 (8,9).…”

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confidence: 99%

Multiple Pathways Are Co-regulated by the Protein Kinase Snf1 and the Transcription Factors Adr1 and Cat8

Young¹,

Dombek²,

Tachibana

et al. 2003

Journal of Biological Chemistry

250

310

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ADR1 and CAT8 encode carbon source-responsive transcriptional regulators that cooperatively control expression of genes involved in ethanol utilization. These transcription factors are active only after the diauxic transition, when glucose is depleted and energy-generating metabolism has shifted to the aerobic oxidation of non-fermentable carbon sources. The Snf1 protein kinase complex is required for activation of their downstream target genes described previously. Using DNA microarrays, we determined the extent to which these three factors collaborate in regulating the expression of the yeast genome after glucose depletion. The expression of 108 genes is significantly decreased in the absence of ADR1. The importance of ADR1 during the diauxic transition is illustrated by the observation that expression of almost one-half of the 40 most highly glucose-repressed genes is ADR1-dependent. ADR1-dependent genes fall into a variety of functional classes with carbon metabolism containing the largest number of members. Most of the genes in this class are involved in the oxidation of different non-fermentable carbon sources. These microarray data show that ADR1 coordinates the biochemical pathways that generate acetylCoA and NADH from non-fermentable substrates. Only a small number of ADR1-dependent genes are also CAT8-dependent. However, nearly one-half of the ADR1-dependent genes are also dependent on the Snf1 protein kinase for derepression. Many more genes are SNF1-dependent than are either ADR1-or CAT8-dependent suggesting that SNF1 plays a broader role in gene expression than either ADR1 or CAT8. The largest class of SNF1-dependent genes encodes regulatory proteins that could extend SNF1 dependence to additional pathways.During the diauxic shift, when yeast cells deplete the glucose in the medium, the flow of metabolites changes dramatically to adapt to the use of alternative energy and carbon sources, primarily ethanol produced during fermentation. The changes in gene expression that are required for this metabolic reorganization were dramatically revealed by DNA microarray analysis (1). The expression of more than one-quarter of the yeast genome is altered when glucose is exhausted. These alterations allow the cell to utilize carbon sources other than glucose to channel metabolites into the tricarboxylic acid and glyoxylate cycles to generate energy and synthesize intermediates for gluconeogenesis. In addition, these changes allow the cell to alter its growth rate and prepare for growth arrest and stationary phase.Numerous transcription factors and regulatory proteins are responsible for the altered transcriptional program that accompanies the depletion of glucose. Two transcription factors that play important roles during the diauxic transition are Adr1 1 and Cat8.

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“…This kinase is an activator of Adr1 and Cat8, which activate expression of genes involved in the diauxic shift, ethanol, and lactate uptake and catabolism, gluconeogenesis, and respiration (17)(18)(19)(20)(21), and is an inhibitor of the Mig1 repressor of glucose-repressed genes (22). SNF1 is a heterotrimer of the Snf1 catalytic subunit, the Snf4 activation subunit (14), and one of three subunits (Sip1, Sip2, and Gal83) that localize SNF1 to different cellular compartments (14,23).…”

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SUMOylation regulates the SNF1 protein kinase

Simpson-Lavy

Johnston

2013

Proc. Natl. Acad. Sci. U.S.A.

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The AMP-activated protein kinase (AMPK) is a major stress sensor of mammalian cells. AMPK's homolog in the yeast Saccharomyces cerevisiae, the SNF1 protein kinase, is a central regulator of carbon metabolism that inhibits the Snf3/Rgt2-Rgt1 glucose sensing pathway and activates genes involved in respiration. We present evidence that glucose induces modification of the Snf1 catalytic subunt of SNF1 with the small ubiquitin-like modifier protein SUMO, catalyzed by the SUMO (E3) ligase Mms21. Our results suggest that SUMOylation of Snf1 inhibits its function in two ways: by interaction of SUMO attached to lysine 549 with a SUMO-interacting sequence motif located near the active site of Snf1, and by targeting Snf1 for destruction via the Slx5-Slx8 (SUMO-directed) ubiquitin ligase. These findings reveal another way SNF1 function is regulated in response to carbon source.protein kinase regulation | protein modification | signal transduction G lucose is the preferred carbon source of most cells, including Saccharomyces cerevisiae, which ferments it to ethanol and CO 2 , producing only two ATPs, even when oxygen is available to drive production of much more ATP. This preference for fermentation (which cancer cells share), is known as the Crabtree or Warburg effect (1, 2). Because of the energetic inefficiency of fermentation, yeast cells must be adroit in sensing glucose. S. cerevisiae has three well-known glucose sensing pathways: (i) the Gpa1/2-Ras2-PKA pathway that regulates stress response (through Msn2/4) and other things; (ii) the SNF1 pathway, which regulates respiratory metabolism and other processes; and (iii) the Snf3/Rgt2-Rgt1 (SRR) pathway that regulates expression of genes encoding hexose transporters (3).The SRR (sensor/receptor-repressor) pathway begins at the cell surface with high-affinity (Snf3) (4) and low-affinity (Rgt2) glucose sensors (5) that are coupled to the casein kinases Yck1 and Yck2, which catalyze phosphorylation of the corepressor proteins Mth1 and Std1 (6), leading to their ubiquitinylation by SCF Grr1 (7,8). The subsequent destruction of Mth1 and Std1 inactivates the Rgt1 transcriptional repressor, resulting in derepression of HXT genes encoding hexose transporters (7, 9). In response to glucose, Yck1/2 also mediates inactivation and degradation of transporters of alternative carbon sources, such as maltose (Mal61) (10) and lactate/pyruvate/acetate (Jen1) (11). Achieving this glucose-induced switching of transporters seems to be the main purpose of the SRR pathway (12).The SNF1 protein kinase-the ortholog of the AMP-activated protein kinase (AMPK), a major stress-activated protein kinase in mammalian cells (13,14)-is a central regulator of carbon metabolism (15,16). This kinase is an activator of Adr1 and Cat8, which activate expression of genes involved in the diauxic shift, ethanol, and lactate uptake and catabolism, gluconeogenesis, and respiration (17-21), and is an inhibitor of the Mig1 repressor of glucose-repressed genes (22). SNF1 is a heterotrimer of the Snf1 catalytic subunit,...

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Adr1 and Cat8 synergistically activate the glucose-regulated alcohol dehydrogenase gene ADH2 of the yeast Saccharomyces cerevisiae

Cited by 55 publications

References 45 publications

Combined Global Localization Analysis and Transcriptome Data Identify Genes That Are Directly Coregulated by Adr1 and Cat8

Combined Global Localization Analysis and Transcriptome Data Identify Genes That Are Directly Coregulated by Adr1 and Cat8

Multiple Pathways Are Co-regulated by the Protein Kinase Snf1 and the Transcription Factors Adr1 and Cat8

SUMOylation regulates the SNF1 protein kinase

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