Evolution of Context Dependent Regulation by Expansion of Feast/Famine Regulatory Proteins [expression]
Ontology highlight
ABSTRACT:
ORGANISM(S): Halobacterium salinarum NRC-1
PROVIDER: GSE61975 | GEO | 2014/10/02
SECONDARY ACCESSION(S): PRJNA262850
REPOSITORIES: GEO
Similar Datasets
Project description:We validated context dependent regulation by two FFRPs AsnC and VNG1237C by deleting the FFRP and testing the effect on downstream target genes. For validtion of AsnC condition specific regulation we grew wild-type and delta-AsnC in the presence of 4mM paraquat (PQ) and samples at 1 and 160 minutes post addition of this sub-lethal dose of PQ. For validation of VNG1237C we grew wild-type and delta-VNG1237C in a standard growth curve sampling at OD 0.18 and 1.15. The asnC deletion strain (M-bM-^HM-^FasnC) and the control M-bM-^HM-^Fura3 strain were grown in 4mM paraquat (PQ) and were sampled at 1 and 160 minutes after PQ addition. Sampling timing for M-bM-^HM-^FVNG1237C was designed such that the starting ODs were as similar as possible and once an OD of 1.17 was reached for M-bM-^HM-^Fura3 the M-bM-^HM-^FVNG1237C was sampled at this same time point.
2014-10-02 | E-GEOD-61975 | biostudies-arrayexpress
Project description:We use RNAseq to compare the transcriptomes of wild type and cells treated with 2.5 mM paraquat (PQ) for 8 hr. We find that PQ treatment results in changes in the transcripts for hundreds of genes. A notable subset of PQ-induced transcripts encodes proteins activated by the retrograde response pathway. This pathway is activated by ETC dysfunction and regulates carbohydrate metabolism to increase synthesis of biosynthetic intermediates through pathways including the TCA cycle, glutamine biosynthetic pathway, and isocitrate metabolism. Transcripts encoding oxidative stress response proteins (e.g. amino acid and iron transporters and siderophores) are also more abundant in PQ-treated cells.
2020-05-19 | GSE150804 | GEO
Project description:To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo.
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Project description:The enzymes of O-GlcNAc cycling couple the nutrient-dependent synthesis of UDP-GlcNAc to O-GlcNAc modification of Ser/Thr residues of key nuclear and cytoplasmic targets. This series of reactions culminating in O-GlcNAcylation of targets has been termed the hexosamine signaling pathway (HSP). The evolutionarily ancient enzymes of O-GlcNAc cycling have co-evolved with other signaling effecter molecules; they are recruited to their targets by many of the same mechanisms used to organize canonic kinase-dependent signaling pathways. This co-recruitment of the enzymes of O-GlcNAc cycling drives a binary switch impacting pathways of anabolism and growth (nutrient uptake) and catabolic pathways (nutrient sparing and salvage). The hexosamine signaling pathway (HSP) has thus emerged as a versatile cellular regulator modulating numerous cellular signaling cascades influencing growth, metabolism, cellular stress, circadian rhythm, and host-pathogen interactions. In mammals, the nutrient-sensing HSP has been harnessed to regulate such cell-specific functions as neutrophil migration, and activation of B-cells and T-cells. This review summarizes the diverse approaches being used to examine O-GlcNAc cycling. It will emphasize the impact O-GlcNAcylation has upon signaling pathways that may be become deregulated in diseases of the immune system, diabetes mellitus, cancer, cardiovascular disease, and neurodegenerative diseases.
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Project description:Not until the turn of this century has immunotherapy become a fundamental component of cancer treatment. While monotherapy with immune modulators, such as immune checkpoint inhibitors, provides a subset of patients with durable clinical benefit and possible cure, combination therapy offers the potential for antitumor activity in a greater number of patients. The field of immunology has provided us with a plethora of potential molecules and pathways to target. This abundance makes it impractical to empirically test all possible combinations efficiently. We recommend that potential immunotherapy combinations be chosen based on sound rationale and available data to address the mechanisms of primary and acquired immune resistance. Novel trial designs may increase the proportion of patients receiving potentially efficacious treatments and, at the same time, better define the balance of clinical activity and safety. We believe that implementing a strategic approach in the early development of immunotherapy combinations will expedite the delivery of more effective therapies with improved safety and durable outcomes.
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Project description:Despite its banishment in several countries, Paraquat (PQ) is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human or animal brain cells such as glial cells or neurons through biological processes as redox by generation of Reactive Oxygen Species (ROS). This specific perturbation has already proven its association for increasing the risk of developing a long-term brain impairment in in vitro and in vivo studies using brain cells. However, there is few evidence of PQ effect on Human Brain Microvascular Endothelial Cells (HBMECs), a particular cell type acting as a macromolecule permeability regulator in the Blood-Brain Barrier (BBB). The present study aimed at unraveling biological mechanisms associated to the exposition of 1, 10 and 100 µM of PQ for 24h on HBMECs. High-throughput mass spectrometry-based proteomics using data-independent acquisition (DIA) was applied. Biological pathway enrichment and cellular assays such as mitochondrial respiration and cholesterol level of PQ-treated HBMECs were performed to verify proteomics results. Proteomic experiment reported a total of 3753 quantified proteins out of which 419 were significantly modulated by paraquat exposure. Biological pathway enrichment revealed that the modified proteins are involved in pathways such as the ubiquinone metabolism, a pathway directly linked to mitochondrial complex I proteins. This study also unveiled the modulation of the cholesterol metabolism. In conclusion, most of the highly differentially expressed proteins (DEPs) in PQ-treated HBMECs were associated to the ubiquinone metabolism pathway confirming the well know mechanism of PQ inducing oxidative stress and inhibit mitochondrial complex I activity. Additionally, this study also described the cholesterol biosynthesis modulation on primary human brain endothelial cells not yet described.
2022-02-17 | PXD026975 | Pride
Project description:BackgroundExpansion of transcription factors is believed to have played a crucial role in evolution of all organisms by enabling them to deal with dynamic environments and colonize new environments. We investigated how the expansion of the Feast/Famine Regulatory Protein (FFRP) or Lrp-like proteins into an eight-member family in Halobacterium salinarum NRC-1 has aided in niche-adaptation of this archaeon to a complex and dynamically changing hypersaline environment.ResultsWe mapped genome-wide binding locations for all eight FFRPs, investigated their preference for binding different effector molecules, and identified the contexts in which they act by analyzing transcriptional responses across 35 growth conditions that mimic different environmental and nutritional conditions this organism is likely to encounter in the wild. Integrative analysis of these data constructed an FFRP regulatory network with conditionally active states that reveal how interrelated variations in DNA-binding domains, effector-molecule preferences, and binding sites in target gene promoters have tuned the functions of each FFRP to the environments in which they act. We demonstrate how conditional regulation of similar genes by two FFRPs, AsnC (an activator) and VNG1237C (a repressor), have striking environment-specific fitness consequences for oxidative stress management and growth, respectively.ConclusionsThis study provides a systems perspective into the evolutionary process by which gene duplication within a transcription factor family contributes to environment-specific adaptation of an organism.
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Project description:The lipocalin Apolipoprotein D (ApoD), known to protect the nervous system against oxidative stress (OS) in model organisms, is up-regulated early in the mouse brain in response to the ROS generator paraquat (PQ). However, the processes triggered by this up-regulation have not been explored.
2011-04-16 | GSE28643 | GEO
Project description:Transcriptomic profiling using Drosophila heads reveals early gene expression responses to transient paraquat exposure. We performed RNAseq profiling of heads from the wild type (WT) Drosophila strain, Canton S (males only), that were fed either 2.5% sucrose (control) or 5 mM PQ in 2.5% sucrose for 12 h.
2019-09-16 | GSE135919 | GEO
Project description:Although evidence accumulates on the role of plant peptides in the response to external conditions, the number of peptide-encoding genes in the genome is still underestimated. In order to identify novel oxidative stress-induced peptides in Arabidopsis thaliana a tiling array analysis (GeneChipM-BM-. Arabidopsis Tiling 1.0R Arrays ) was performed on mRNA extracted from leaves treated with paraquat (PQ), an reactive oxygen species inducer and water (control), resulting in the identification of 92,844 and 86,272 transcriptionally active regions (TARs), respectively. Normalized log signals were obtained using the Affymetrix Tiling Analysis Software - Version 1.1, Build 2. ON and OFF probes were selected using a treshold, based on positive controls. Next, groups of 4-13 successive ON probes were combined into short TARs and a selection was made of TARs having an average signal intensity at least 2.6-fold higher after PQ treatment compared to the control treatment, resulting in 176 TARS induced by PQ. paraquat treated A. thaliana leaves (2 replicates) vs control (water) treated A. thaliana leaves (2 replicates), (4 samples in total)
2013-08-31 | E-GEOD-49001 | biostudies-arrayexpress