ArticleMolecular and cellular biology2002
The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 209 citations in OpenAlex.
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- Signaling pathways regulating VDAC1 overexpression associated with apoptosis, pyroptosis, and ferroptosis.Cell communication and signaling : CCS · 2026Article
- Insight into the Regulation of NDRG1 Expression.International journal of molecular sciences · 2025Review
- HIF-1α Promotes Luteinization via NDRG1 Induction in the Human Ovary.Biomedicines · 2025Article
- Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.Science advances · 2023Review
- Chromosome-level genome assembly and population genomics of Mongolian racerunner (Eremias argus) provide insights into high-altitude adaptation in lizards.BMC biology · 2023Article
- The Beneficial Effect of the Blockade of Stim-Activated TRPC-ORAI Channels on Vascular Remodeling and Pulmonary Hypertension Induced by Intermittent Hypoxia Is Independent of Oxidative Stress.Advances in experimental medicine and biology · 2023Article
- Hypoxia-inducible factor signaling in vascular calcification in chronic kidney disease patients.Journal of nephrology · 2022Review
- P4HA2: A link between tumor-intrinsic hypoxia, partial EMT and collective migration.Advances in cancer biology - metastasis · 2022Article
- A Tumor Suppressor Gene, N-myc Downstream-Regulated Gene 1 (NDRG1), in Gliomas and Glioblastomas.Brain sciences · 2022Review
- Arbitrary CaFrontiers in pharmacology · 2022Article
- Crucial Role of Stromal Interaction Molecule-Activated TRPC-ORAI Channels in Vascular Remodeling and Pulmonary Hypertension Induced by Intermittent Hypoxia.Frontiers in physiology · 2022Article
- Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms.International journal of molecular sciences · 2021Review
- The Relationship of Glutathione-Molecules (Basel, Switzerland) · 2021Review
- The Oncogenic Signaling Disruptor, NDRG1: Molecular and Cellular Mechanisms of Activity.Cells · 2021Review
- Review
- Molecular Characterization of NDL1-AGB1 Mediated Salt Stress Signaling: Further Exploration of the Role ofCells · 2021Article
- Article
- LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression.PeerJ · 2020Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Hypoxia causes the accumulation of the transcription factor hypoxia-inducible factor 1 (HIF-1), culminating in the expression of hypoxia-inducible genes such as those for vascular endothelial growth factor (VEGF) and NDRG-1/Cap43. Previously, we have demonstrated that intracellular calcium (Ca(2+)) is required for the expression of hypoxia-inducible genes. Here we found that, unlike with hypoxia or hypoxia-mimicking conditions, the elevation of intracellular Ca(2+) neither induced the HIF-1alpha protein nor stimulated HIF-1-dependent transcription. Furthermore, the elevation of intracellular Ca(2+) induced NDRG-1/Cap43 mRNA in HIF-1alpha-deficient cells. It also increased levels of c-Jun protein, causing its phosphorylation. The protein kinase inhibitor K252a abolished c-Jun induction and activator protein 1 (AP-1)-dependent reporter expression caused by Ca(2+) ionophore or hypoxia. K252a also significantly decreased hypoxia-induced VEGF and NDRG-1/Cap43 gene expression in both human and mouse cells. Using a set of deletion VEGF-Luc promoter constructs, we found that both HIF-1 and two AP-1 sites contribute to hypoxia-mediated induction of transcription. In contrast, only AP-1 sites contributed to Ca(2+)-mediated VEGF-Luc induction. A dominant-negative AP-1 prevented Ca(2+)-dependent transcription and partially impaired hypoxia-mediated transcription. In addition, dominant-negative AP-1 diminished the expression of the NDRG-1/Cap43 gene following hypoxia. We conclude that during hypoxia, an increase in intracellular Ca(2+) activates a HIF-1-independent signaling pathway that involves AP-1-dependent transcription. Cooperation between the HIF-1 and AP-1 pathways allows fine regulation of gene expression during hypoxia.
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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.