Receptor-mediated endoproteolytic activation of two transcription factors in yeast

Andréasson, Claes; Ljungdahl, Per O.

doi:10.1101/gad.239202

Cited by 113 publications

(177 citation statements)

References 42 publications

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“…This pathway derives its name from the three core components of the plasma membrane-localized SPS sensor, i.e., Ssy1, Ptr3, and Ssy5 (Forsberg and Ljungdahl 2001a). The SPS sensor regulates gene expression by controlling the activity of two transcription factors, Stp1 and Stp2 ( Figure 11A) (Andréasson and Ljungdahl 2002). These factors are synthesized as latent cytoplasmic proteins with N-terminal regulatory domains that function as nuclear exclusion determinants .…”

Section: Pathway Genesmentioning

confidence: 99%

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

2012

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Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear.

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Section: Pathway Genesmentioning

confidence: 99%

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

2012

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“…Stp1 and Stp2 have been proposed to play redundant roles in the SPS amino acid sensing pathway (18,(21)(22)(23). However, a recent publication suggests that Stp1 and Stp2 are derived from a genome duplication event that occurred in a yeast ancestor and functionally diverged during evolution (25).…”

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confidence: 99%

“…The positive regulatory function of Grr1 and Cdc34 in this pathway appears to promote amino acid-induced processing of Stp1 (8). However, Stp1 processing is independent of proteasome function, indicating that Grr1/Cdc34-dependent processing of Stp1 requires ubiquitination but not proteasome-dependent degradation (8,18).…”

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confidence: 99%

Differential Regulation of Transcription Factors Stp1 and Stp2 in the Ssy1-Ptr3-Ssy5 Amino Acid Sensing Pathway

Tumusiime

Zhang

Overstreet

et al. 2011

Journal of Biological Chemistry

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Stp1 and Stp2 are two homologous transcription factors activated in response to extracellular amino acid stimuli. Here we show that both ubiquitin-dependent degradation of Stp1 and Stp2 and their intracellular localization are differentially regulated. We have found that the E2 ubiquitinconjugating enzyme Cdc34 is required for degradation of both full-length and processed Stp1, but not Stp2. We have also found that Grr1, the F-box component of the SCF Grr1 E3 ubiquitin ligase, is the primary factor in degradation of full-length Stp1, whereas both Grr1 and Cdc4 are required for degradation of processed Stp1. Our localization studies showed that full-length Stp1 is localized both in the cytoplasm and at the cell periphery, whereas full-length Stp2 is localized only diffusely in the cytoplasm. We identified two nuclear localization signals of Stp1 and found that the Nterminal domain of Stp1 is required for localization of fulllength Stp1 to the cell periphery. We also found that Stp2 is the primary factor involved in basal activation of target gene expression. Our results indicate that the functions of two seemingly redundant transcription factors can be separated by differential degradation and distinct cellular localization.

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“…Most amino acids present in the external medium are detected by yeast cells via a membrane-associated sensor complex (Ssy1-Ptr3-Ssy5 [SPS]) made of three proteins, including Ssy1, an amino acid permease homolog devoid of transport activity (15,46). This SPS complex in turn activates the transcription of several amino acid permease genes via the Stp1, Stp2, and Uga35/Dal81 transcription factors (1,5,63). Putative additional target genes of this transcriptional control system have emerged from several genomic studies aiming to list all genes induced by amino acids in a Ssy1-, Stp1-, and/or Stp2-dependent manner (43,45,73).…”

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confidence: 99%

Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

Godard

Urrestarazu

Vissers

et al. 2007

Molecular and Cellular Biology

220

270

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We compared the transcriptomes of Saccharomyces cerevisiae cells growing under steady-state conditions on 21 unique sources of nitrogen. We found 506 genes differentially regulated by nitrogen and estimated the activation degrees of all identified nitrogen-responding transcriptional controls according to the nitrogen source. One main group of nitrogenous compounds supports fast growth and a highly active nitrogen catabolite repression (NCR) control. Catabolism of these compounds typically yields carbon derivatives directly assimilable by a cell's metabolism. Another group of nitrogen compounds supports slower growth, is associated with excretion by cells of nonmetabolizable carbon compounds such as fusel oils, and is characterized by activation of the general control of amino acid biosynthesis (GAAC). Furthermore, NCR and GAAC appear interlinked, since expression of the GCN4 gene encoding the transcription factor that mediates GAAC is subject to NCR. We also observed that several transcriptional-regulation systems are active under a wider range of nitrogen supply conditions than anticipated. Other transcriptional-regulation systems acting on genes not involved in nitrogen metabolism, e.g., the pleiotropic-drug resistance and the unfolded-protein response systems, also respond to nitrogen. We have completed the lists of target genes of several nitrogen-sensitive regulons and have used sequence comparison tools to propose functions for about 20 orphan genes. Similar studies conducted for other nutrients should provide a more complete view of alternative metabolic pathways in yeast and contribute to the attribution of functions to many other orphan genes.

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Receptor-mediated endoproteolytic activation of two transcription factors in yeast

Cited by 113 publications

References 42 publications

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

Differential Regulation of Transcription Factors Stp1 and Stp2 in the Ssy1-Ptr3-Ssy5 Amino Acid Sensing Pathway

Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

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