ArticleMolecular and cellular biology2007
The ternary complex factor net is downregulated by hypoxia and regulates hypoxia-responsive genes.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- ETS transcription factor ELK3: Molecular insights and translational horizons in cancer (Review).Oncology letters · 2026Review
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- ELK3 destabilization by speckle-type POZ protein suppresses prostate cancer progression and docetaxel resistance.Cell death & disease · 2024Article
- Epigenetics and stroke: role of DNA methylation and effect of aging on blood-brain barrier recovery.Fluids and barriers of the CNS · 2023Article
- Epigenetics and stroke: role of DNA methylation and effect of aging on blood-brain barrier recovery.Research square · 2023Article
- Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development.International journal of molecular sciences · 2021Review
- Approaches to develop therapeutics to treat frontotemporal dementia.Neuropharmacology · 2020Review
- RSK2-Mediated ELK3 Activation Enhances Cell Transformation and Breast Cancer Cell Growth by Regulation of c-fos Promoter Activity.International journal of molecular sciences · 2019Article
- XRP44X, an Inhibitor of Ras/Erk Activation of the Transcription Factor Elk3, Inhibits Tumour Growth and Metastasis in Mice.PloS one · 2016Article
- Elk-3 is a KLF4-regulated gene that modulates the phagocytosis of bacteria by macrophages.Journal of leukocyte biology · 2015Article
- The oncogenic MicroRNA Hsa-miR-155-5p targets the transcription factor ELK3 and links it to the hypoxia response.PloS one · 2014Article
- Endothelial SRF/MRTF ablation causes vascular disease phenotypes in murine retinae.The Journal of clinical investigation · 2013Article
- Article
- Involvement of net and Hif1alpha in distinct yet intricately linked hypoxia-induced signaling pathways.The Journal of biological chemistry · 2010Article
- The expression of ELK transcription factors in adult DRG: Novel isoforms, antisense transcripts and upregulation by nerve damage.Molecular and cellular neurosciences · 2010Article
- Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension.Pulmonary circulationArticle
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia and the Net ternary complex factor (TCF) regulate similar processes (angiogenesis, wound healing, and cellular migration) and genes (PAI-1, c-fos, erg-1, NOS-2, HO-1, and vascular endothelial growth factor genes), suggesting that they are involved in related pathways. We show here that hypoxia regulates Net differently from the other TCFs and that Net plays a role in the hypoxic response in vivo in mice and in cells. Hypoxia induces Net depletion from target promoters, nuclear export, ubiquitylation, and proteasomal degradation. Key mediators of the hypoxic response, the prolyl-4-hydroxylases containing domain proteins (PHDs), regulate Net. PHD downregulation in normoxia leads to Net degradation, and PHD overexpression delays Net downregulation by hypoxia. Net inhibition by RNA interference or mutation leads to altered regulation by hypoxia of the Net targets PAI-1, c-fos, and egr-1. We propose that hypoxia stimulates transcription of target promoters through removal of the repressor function of Net. Interestingly, the hematocrit response to a chemical inducer of hypoxia-like responses (cobalt chloride) is strongly altered in Net mutant mice. Our results show that the Net TCF is part of the biological response to hypoxia, adding a new component to an important pathological and physiological process.
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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 Socratic graph.