Glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene occurs by a cAMP signaling pathway.

Hoffman, Charles S.; Winston, Fred

doi:10.1101/gad.5.4.561

Cited by 148 publications

(153 citation statements)

References 61 publications

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“…Furthermore, as shown in Figure 3D, the Gad8 phosphorylation was not induced in glucose-starved cells after being treated with 5 mM cAMP, which is known to activate PKA in S. pombe. 40 It is therefore unlikely that the cAMP-PKA pathway mediates glucose signals to control the TORC2 activity. Gad8 is immediately dephosphorylated upon glucose depletion in the growth medium.…”

Section: Glucose-regulation Of the Ryh1 Gtpase Contributes To Torc2 Amentioning

confidence: 99%

“…Our mutational analysis indicated that the glucose regulation of fission yeast TORC2 is not dependent on the cAMP pathway, a signaling mechanism known to be responsive to extracellular glucose. [39][40][41][42] Importantly, glucose-replete conditions increase the active, GTP-bound form of Ryh1 GTPase, which induces TORC2-dependent phosphorylation of Gad8. Glucose starvation swiftly inactivates Ryh1 and suppresses the TORC2-Gad8 pathway, which is, however, gradually reactivated in a manner independent of Ryh1.…”

Section: Introductionmentioning

confidence: 99%

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Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose

et al. 2015

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The Target Of Rapamycin (TOR) is an evolutionarily conserved protein kinase that forms 2 distinct protein complexes referred to as TOR complex 1 (TORC1) and 2 (TORC2). Recent extensive studies have demonstrated that TORC1 is under the control of the small GTPases Rheb and Rag that funnel multiple input signals including those derived from nutritional sources; however, information is scarce as to the regulation of TORC2. A previous study using the model system provided by the fission yeast Schizosaccharomyces pombe identified Ryh1, a Rab-family GTPase, as an activator of TORC2. Here, we show that the nucleotide-binding state of Ryh1 is regulated in response to glucose, mediating this major nutrient signal to TORC2. In glucose-rich growth media, the GTP-bound form of Ryh1 induces TORC2-dependent phosphorylation of Gad8, a downstream target of TORC2 in fission yeast. Upon glucose deprivation, Ryh1 becomes inactive, which turns off the TORC2-Gad8 pathway. During glucose starvation, however, Gad8 phosphorylation by TORC2 gradually recovers independently of Ryh1, implying an additional TORC2 activator that is regulated negatively by glucose. The paired positive and negative regulatory mechanisms may allow fine-tuning of the TORC2-Gad8 pathway, which is essential for growth under glucose-limited environment.

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Section: Glucose-regulation Of the Ryh1 Gtpase Contributes To Torc2 Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose

et al. 2015

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“…Expression of the S. pombe fbp1 gene, encoding fructose 1,6-bisphosphatase, was reported to be repressed in 8% glucose (36) because of regulation by a glucose-induced cAMP signal (37). The increased expression of mae2 observed in high concentrations of glucose (and therefore high cAMP levels) suggested that cAMP induction may be involved in this response.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Regulation of the Schizosaccharomyces pombe Malic Enzyme Gene, mae2

Viljoen

Volschenk

Young

et al. 1999

Journal of Biological Chemistry

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The NAD-dependent malic enzyme from Schizosaccharomyces pombe catalyzes the oxidative decarboxylation of L-malate to pyruvate and CO 2 . Transcription of the S. pombe malic enzyme gene, mae2, was studied to elucidate the regulatory mechanisms involved in the expression of the gene. No evidence for substrate-induced expression of mae2 was observed in the presence of 0.2% L-malate. However, transcription of mae2 was induced when cells were grown in high concentrations of glucose or under anaerobic conditions. The increased levels of malic enzyme may provide additional pyruvate or assist in maintaining the redox potential under fermentative conditions. Deletion and mutation analyses of the 5-flanking region of the mae2 gene revealed the presence of three novel negative cis-acting elements, URS1, URS2, and URS3, that seem to function cooperatively to repress transcription of the mae2 gene. URS1 and URS2 are also present in the promoter region of the S. pombe malate transporter gene, suggesting co-regulation of their expression. Furthermore, two positive cisacting elements in the mae2 promoter, UAS1 and UAS2, show homology with the DNA recognition sites of the cAMP-dependent transcription factors ADR1, AP-2, and ATF (activating transcription factor)/CREB (cAMP response element binding).The fission yeast Schizosaccharomyces pombe efficiently degrades L-malate to CO 2 under aerobic conditions and to ethanol and CO 2 under anaerobic conditions (1). Cells of S. pombe are not able to utilize malate as the sole energy source or incorporate the malate into biomass (2) and therefore require glucose or other carbon sources for the energy-dependent transport and efficient degradation of malic acid (3). Three enzymes are involved in malate degradation in S. pombe, namely the malate transporter, malic enzyme, and malate dehydrogenase (4). The transporter, encoded by the mae1 gene (5), uses an H ϩ -symport system for the active transport of L-malate, and the NAD-dependent malic enzyme (EC 1.1.1.38) catalyzes the oxidative decarboxylation of L-malate to pyruvate and CO 2 . The mitochondrial malate dehydrogenase oxidizes L-malate to oxaloacetate in the tricarboxylic acid cycle and is responsible for 10% of the degradation of malate under aerobic conditions. Molecular analysis of the S. pombe malic mae2 gene showed a high degree of homology with malic enzymes from various organisms (6). Eight highly conserved regions were identified in malic enzymes, including the binding sites for L-malate and the dinucleotide co-factors NAD(P) ϩ (7,8). Although the secondary structure of malic enzymes is highly conserved, the coenzyme specificity (NAD ϩ or NADP ϩ ) and cellular localization (cytosolic or mitochondrial) are strongly linked to their regulation and metabolic function (9). Cytosolic NADP-dependent malic enzymes play an important role in lipid metabolism in higher eukaryotes (10), whereas NAD-dependent malic enzymes provide mitochondrial NADH for electron transport or cytosolic NADH for reductive power for other metabolic pathways (9)....

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“…This collection of mutants includes 31 strains carrying mutations in the git2 1 / cyr1 1 adenylate cyclase gene, some of which compose two intragenic complementation groups (Hoffman andWinston 1990, 1991). In vitro assays of adenylate cyclase activity showed wild-type catalytic activity in git2-7 and git2-210 strains from one group and reduced catalytic activity in a git2-61 strain from the second group (Hoffman and Winston 1991). Presumably, the first group is defective in a step involved in in vivo activation, such as binding an activator, while the second group is defective in catalytic activity.…”

Section: R176hmentioning

confidence: 99%

“…However, S. pombe Gpa2, which has recently been shown to directly bind an N-terminal domain of adenylate cyclase (Ivey and Hoffman 2005), functions together with the Git5-Git11 Gbg dimer (Landry et al 2000;Landry and Hoffman 2001), while the only authentic S. cerevisiae Gbg dimer, Ste4-Ste18, does not act in conjunction with Gpa2 (Liu et al 1993). In addition, Ras proteins play an important role in adenylate cyclase activation in S. cerevisiae, but have no role in the S. pombe cAMP pathway (Toda et al 1985;Fukui et al 1986;Mbonyi et al 1988;Hoffman and Winston 1991).…”

Section: R176hmentioning

confidence: 99%

Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling

Wang

Griffiths²,

Zhang

et al. 2005

Genetics

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Mutations affecting the Schizosaccharomyces pombe cAMP phosphodiesterase (PDE) gene cgs2 1 were identified in a screen for suppressors of mutant alleles of the adenylate cyclase gene (git2 1 /cyr1 1 ), which encode catalytically active forms of the enzyme that cannot be stimulated by extracellular glucose signaling. These mutations suppress both the git2 ÿ mutant alleles used in the suppressor selection and mutations in git1, and git11 1 , which are all required for adenylate cyclase activation. Notably, these cgs2 mutant alleles fail to suppress mutations in gpa2 1 , which encodes the Ga subunit of a heterotrimeric G protein required for adenylate cyclase activation, although the previously identified cgs2-2 allele does suppress loss of gpa2 1. Further analysis of the cgs2-s1 allele reveals a synthetic interaction with the gpa2 R176H-activated allele, with respect to derepression of fbp1-lacZ transcription in glucose-starved cells. In addition, direct measurements of cAMP levels show that cgs2-s1 cells maintain normal basal cAMP levels, but are severely defective in feedback regulation upon glucose detection. These results suggest that PDE activity in S. pombe may be coordinately regulated with adenylate cyclase activity as part of the feedback regulation mechanism to limit the cAMP response to glucose detection.

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Glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene occurs by a cAMP signaling pathway.

Cited by 148 publications

References 61 publications

Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose

Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose

Transcriptional Regulation of the Schizosaccharomyces pombe Malic Enzyme Gene, mae2

Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling

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