ArticleGenetics2009
Two distinct roles for EGL-9 in the regulation of HIF-1-mediated gene expression in Caenorhabditis elegans.
Article in Genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 70 citations in OpenAlex.
- Forward genetics ineLife · 2025Article
- The mayfly Neocloeon triangulifer senses decreasing oxygen availability (PO2) and responds by reducing ion uptake and altering gene expression.The Journal of experimental biology · 2024Article
- Fmo induction as a tool to screen for pro-longevity drugs.GeroScience · 2024Article
- Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis ineLife · 2024Article
- Transcriptome analyses describe the consequences of persistent HIF-1 over-activation in Caenorhabditis elegans.PloS one · 2024Article
- Article
- Whole genome profiling of short-term hypoxia induced genes and identification of HIF-1 binding sites provide insights into HIF-1 function inbioRxiv : the preprint server for biology · 2023Article
- Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis inbioRxiv : the preprint server for biology · 2023Article
- Assessing the PThe Science of the total environment · 2022Article
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Identification of enzymes that have helminth-specific active sites and are required for Rhodoquinone-dependent metabolism as targets for new anthelmintics.PLoS neglected tropical diseases · 2021Article
- Crosstalk in oxygen homeostasis networks: SKN-1/NRF inhibits the HIF-1 hypoxia-inducible factor in Caenorhabditis elegans.PloS one · 2021Article
- Hypoxic response regulators RHY-1 and EGL-9/PHD promote longevity through a VHL-1-independent transcriptional response.GeroScience · 2020Article
- HIF-1 Has a Central Role inFrontiers in genetics · 2020Article
- Ferritin is regulated by a neuro-intestinal axis in the nematode Caenorhabditis elegans.Redox biology · 2020Article
- The hypoxia-response pathway modulates RAS/MAPK-mediated cell fate decisions inLife science alliance · 2019Article
- Reconstructing a metazoan genetic pathway with transcriptome-wide epistasis measurements.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α.Molecular and cellular biology · 2016Article
- A HIF-independent mediator of transcriptional responses to oxygen deprivation in Caenorhabditis elegans.Genetics · 2015Article
- A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis.PloS one · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Oxygen is critically important to metazoan life, and the EGL-9/PHD enzymes are key regulators of hypoxia (low oxygen) response. When oxygen levels are high, the EGL-9/PHD proteins hydroxylate hypoxia-inducible factor (HIF) transcription factors. Once hydroxylated, HIFalpha subunits bind to von Hippel-Lindau (VHL) E3 ligases and are degraded. Prior genetic analyses in Caenorhabditis elegans had shown that EGL-9 also acted through a vhl-1-independent pathway to inhibit HIF-1 transcriptional activity. Here, we characterize this novel EGL-9 function. We employ an array of complementary methods to inhibit EGL-9 hydroxylase activity in vivo. These include hypoxia, hydroxylase inhibitors, mutation of the proline in HIF-1 that is normally modified by EGL-9, and mutation of the EGL-9 catalytic core. Remarkably, we find that each of these treatments or mutations eliminates oxygen-dependent degradation of HIF-1 protein, but none of them abolishes EGL-9-mediated repression of HIF-1 transcriptional activity. Further, analyses of new egl-9 alleles reveal that the evolutionarily conserved EGL-9 MYND zinc finger domain does not have a major role in HIF-1 regulation. We conclude that C. elegans EGL-9 is a bifunctional protein. In addition to its well-established role as the oxygen sensor that regulates HIF-1 protein levels, EGL-9 inhibits HIF-1 transcriptional activity via a pathway that has little or no requirement for hydroxylase activity or for the EGL-9 MYND domain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.