Two nutrient sensing and regulatory pathways, the general amino acid control (GAAC) and the target of rapamycin (TOR), control yeast growth and metabolism in response to changes in nutrient availability. Starvation for amino acids activates the GAAC pathway, involving Gcn2p phosphorylation of eIF2 and preferential translation of GCN4, a transcription activator of genes involved in amino acid metabolism. TOR senses nitrogen availability and regulates gene expression through transcription factors, such as Gln3p. We used microarray analyses to address the integration of the GAAC and TOR pathways in directing the yeast transcriptome in response to amino acid starvation and rapamycin treatment. Of the ~2500 genes whose expression was changed by 2-fold or greater, Gcn4p and Gln3p were required for 542 and 657 genes, respectively. While Gcn4p activates a common core of 57 genes in response to amino acid starvation or rapamycin treatment, the different stress arrangements allow for variations in Gcn4p-directed transcription. With few exceptions, genes requiring Gcn2p eIF2 kinase for induced expression also required Gcn4p, emphasizing the role of Gcn2p as an upstream activator of Gcn4p-directed transcription. There is also significant coordination between the GAAC and TOR pathways, with Gcn4p being required for activation of more genes during rapamycin treatment than Gln3p. Importantly, TOR regulates the GAAC-directed transcription of genes required for assimilation of nitrogen sources, such as -amino-butyric acid. Therefore, yeast has integrated gene expression responses to amino acid abundance and nitrogen source quality through the control of Gcn2p phosphorylation of eIF2 and GCN4 translation.
Integration of general amino acid control and target of rapamycin (TOR) regulatory pathways in nitrogen assimilation in yeast.
Treatment
View SamplesHere we examined virulence activation in Pseudomonas aeruginosa in response to the synthetic kappa opioid agonist U-50, 488 in nutrient poor media where growth conditions are limited and density dependent quorum sensing is not activated.
Pseudomonas aeruginosa overrides the virulence inducing effect of opioids when it senses an abundance of phosphate.
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View SamplesDuring extreme physiological stress, the intestinal tract can be transformed into a harsh environment characterized by regio- spatial alterations in oxygen, pH, and phosphate concentration. When the human intestine is exposed to extreme medical interventions, the normal flora becomes replaced by pathogenic species whose virulence can be triggered by various physico-chemical cues leading to lethal sepsis. We previously demonstrated that phosphate depletion develops in the mouse intestine following surgical injury and triggers intestinal P. aeruginosa to express a lethal phenotype that can be prevented by oral phosphate ([Pi]) supplementation.
Prevention of siderophore- mediated gut-derived sepsis due to P. aeruginosa can be achieved without iron provision by maintaining local phosphate abundance: role of pH.
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View SamplesP. aeruginosa PAO1 grown as lawns on Nematode Growth Medium prepared without supplementation (NGM Pi<0.1 mM) has high killing ability against C. elegans, however, no mortality in worms has been observed during 48 hrs when feeding on PAO1 lawns grown on phosphate supplemented full NGM Pi 25 mM, pH 6.0 medium.
Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Specimen part, Cell line
View SamplesTumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-II and the subsequent activation of NF-B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC- knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-II- NF-B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Specimen part
View SamplesTumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-II and the subsequent activation of NF-B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC- knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-II- NF-B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Specimen part, Cell line
View SamplesWound infections are traditionally thought to occur when microbial burden exceeds the innate clearance capacity of host immune system. Here we introduce the idea that the wound environment itself plays a significant contributory role to wound infection.
Pseudomonas aeruginosa wound infection involves activation of its iron acquisition system in response to fascial contact.
No sample metadata fields
View SamplesWilliams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by aa 1.5 Mb microdeletion on human chromosome 7. Although the molecular cause of the disorder is well-established, little is known about the global impact of the deletion on gene expression. Here we profiled the transcriptomes of fibroblast cell lines from 8 young girls with WBS, and 9 sex- and age-matched control individuals
Using transcription modules to identify expression clusters perturbed in Williams-Beuren syndrome.
Sex, Cell line
View SamplesMetastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell-cell and cell-matrix interactions. CD146 (MCAM) is associated with advanced tumor stage in melanoma, prostate and ovarian cancers.
CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines.
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