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The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

ABSTRACT: The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

PROVIDER: PRJNA726196 | ENA |

REPOSITORIES: ENA

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ChIP-Seq Files : The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

Project description:ChIP-Seq Files : The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

| PRJNA725199 | ENA

RNA-seq Files : The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

Project description:RNA-seq Files : The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

| PRJNA726201 | ENA

The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans.

Project description:Actively dividing cells, including some cancers, rely on aerobic glycolysis rather than oxidative phosphorylation to generate energy, a phenomenon termed the Warburg effect. Constitutive activation of the Hypoxia Inducible Factor (HIF-1), a transcription factor known for mediating an adaptive response to oxygen deprivation (hypoxia), is a hallmark of the Warburg effect. HIF-1 is thought to promote glycolysis and suppress oxidative phosphorylation. Here, we instead show that HIF-1 can promote gluconeogenesis. Using a multiomics approach, we reveal the genomic, transcriptomic, and metabolomic landscapes regulated by constitutively active HIF-1 in C. elegans. We use RNA-seq and ChIP-seq under aerobic conditions to analyze mutants lacking EGL-9, a key negative regulator of HIF-1. We integrate these approaches to identify over two hundred genes directly and functionally upregulated by HIF-1, including the PEP carboxykinase PCK-1, a rate-limiting mediator of gluconeogenesis. This activation of PCK-1 by HIF-1 promotes survival in response to both oxidative and hypoxic stress. Our work identifies functional direct targets of HIF-1 in vivo, comprehensively describing the metabolome induced by HIF-1 activation in an organism.

| S-EPMC9579151 | biostudies-literature

The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-19 | GSE173581 | GEO

Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) regulates metabolic adaptation and glucose-independent tumor cell growth

Project description:Cancer cells must adapt metabolically to survive and proliferate when nutrients are limiting. Here we used combined transcriptional-metabolomic network analysis to identify metabolic pathways that support glucose-independent tumor cell growth. We found that glucose deprivation stimulated the re-wiring of the tricarboxylic acid (TCA) cycle and co-opting early steps of gluconeogenesis to promote cell proliferation under low glucose. Glucose limitation promoted the production of phosphoenolpyruvate (PEP) from glutamine, which was used to fuel biosynthetic pathways normally sustained by glucose, including serine and purine biosynthesis. Mitochondrial PEP-carboxykinase (PCK2) was required for this glutamine-dependent metabolic reprogramming. PCK2 expression was dependent on the hypoxia-inducible factors (HIFs), and required to maintain tumor cell proliferation under limiting glucose availability. Elevated PCK2 expression is observed in several human tumor types, and enriched in tumor tissue from non-small cell lung cancer (NSCLC) patients. Our results define a novel role for PCK2 in cancer cell metabolic reprogramming that promotes glucose-independent cell growth and metabolic stress resistance in human tumors.

2015-10-15 | GSE66556 | GEO

RNA-seq Files : The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

Project description:RNA was isolated from L4 stage animals for the following genotypes: N2, hif-1(ia4), egl-9(sa307), hif-1(ia4);egl-9(sa307) grown at 20C. Total RNA was isolated and used to prepare libraries using the Illumina Truseq with polyA selection. Libraries were sequenced across two lanes on an Illumina HiSeq2000 (GeneWiz) or an Illumina HiSeq 2500 in Rapid Run Mode (RUCDR).

2022-09-19 | GSE173580 | GEO

ChIP-Seq Files : The Hypoxia Response Pathway Promotes PEP Carboxykinase And Gluconeogenesis In C. elegans

Project description:To identify genes directly regulated by HIF-1, we performed ChIP-seq on L4-stage egl-9(sa307); hif-1(ia4); odIs131[hif-1::gfp] animals, which have activated HIF-1 under aerobic conditions, using anti-GFP antibodies to precipitate DNA bound by HIF-1::GFP followed by high-throughput sequencing to identify peaks of reads corresponding to HIF-1 binding sites

2022-09-19 | GSE173333 | GEO

SHP-1 regulates transcription of PCK1 to control gluconeogenesis

Project description:The protein-tyrosine phosphatase SHP-1 (PTPN6) is an important glucose homeostasis modulator. Besides negatively regulating insulin signaling, the specific role of SHP-1 in metabolic control remains poorly understood. We show that SHP-1 acts as a co-activator for transcription of the phosphoenolpyruvate carboxykinase 1 (PCK1) gene, thereby modulating basal gluconeogenesis in hepatocytes. SHP-1 interacts with RNA polymerase II-subunits and signal transducer and activator of transcription 5 (STAT5), and localizes to the nucleus, where a sub-fraction of SHP-1 associates with chromatin. While SHP-1 binds to the PCK1-promoter, its loss affects RNA polymerase II-recruitment to this and other promoters of genes enriched for glucose metabolism-related functions. SHP-1-downregulation, and similarly STAT5 pharmacological inhibition reduce PCK1-transcript levels correlating with blunted gluconeogenesis. Overall, we identified a novel molecular SHP-1-function, that of a regulator of PCK1-transcription and subsequently hepatic gluconeogenesis, through physical interaction with the transcription machinery, mediated by an Akt-independent mechanism, but independent of STAT5 tyrosine-phosphorylation status.

2023-09-08 | GSE174142 | GEO

Phylogenetic study of the evolution of PEP-carboxykinase.

Project description:Phosphoenolpyruvate carboxykinase (PCK) is the key enzyme to initiate the gluconeogenic pathway in vertebrates, yeast, plants and most bacteria. Nucleotide specificity divided all PCKs into two groups. All the eukaryotic mammalian and most archaeal PCKs are GTP-specific. Bacterial and fungal PCKs can be ATP-or GTP-specific but all plant PCKs are ATP-specific. Amino acid sequence alignment of PCK enzymes shows that the nucleotide binding sites are somewhat conserved within each class with few exceptions that do not have any clear ATP- or GTP-specific binding motif. Although the active site residues are mostly conserved in all PCKs, not much significant sequence homology persists between ATP- and GTP-dependent PCK enzymes. There is only one planctomycetes PCK enzyme (from Cadidatus Kuenenia stuttgartiensis) that shows sequence homology with both ATP-and GTP-dependent PCKs. Phylogenetic studies have been performed to understand the evolutionary relationship of various PCKs from different sources. Based on this study a flowchart of the evolution of PCK has been proposed.

| S-EPMC2684135 | biostudies-literature

Reply to: Potential contribution of PEP carboxykinase-dependent malate dismutation to the hypoxia response in C. elegans.

Project description: Not available

| S-EPMC10319873 | biostudies-literature