ArticleMolecular biology of the cell2011
Hypoxia-inducible factor-1α mRNA: a new target for destabilization by tristetraprolin in endothelial cells.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Expression of Hypoxia-Inducible Factor1-α in Varicocele Disease: a Comprehensive Systematic Review.Reproductive sciences (Thousand Oaks, Calif.) · 2022Pooled it
- Translational development of ABCB5Stem cell research & therapy · 2022Trial
- Article
- Sequence-specific targeting of VEGFA genomic DNA to inhibit tumor growth.NPJ precision oncology · 2026Article
- Key role of transcription factors network in proliferative vitreoretinal diseases development.Cell & bioscience · 2026Review
- A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Decoding the hypoxic injury landscape and hypoxic risk model construction in diabetic kidney disease: a multi-omics study.Frontiers in bioinformatics · 2026Article
- Biological Regulation of HIF-1α and Its Role in Therapeutic Angiogenesis for Treatment of Ischemic Cardiovascular Disease.International journal of molecular sciences · 2025Review
- Transcriptomic and Metabolomic Insights into Age-Related Changes in Lung Tissue of Yaks Under Highland Stress.International journal of molecular sciences · 2024Article
- IFI16 Is Indispensable for Promoting HIF-1α-Mediated APOL1 Expression in Human Podocytes under Hypoxic Conditions.International journal of molecular sciences · 2024Article
- Effect of the antirheumatic medication methotrexate (MTX) on biomechanical compressed human periodontal ligament fibroblasts (hPDLFs).BMC oral health · 2024Article
- Potential Impact of Hypoxic Astrocytes on the Aggravation of Depressive Symptoms in Parkinson's Disease.Journal of molecular neuroscience : MN · 2024Article
- Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis.Cell death discovery · 2024Article
- Hypoxia-Induced Changes in L-Cysteine Metabolism and Antioxidative Processes in Melanoma Cells.Biomolecules · 2023Article
- Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism.Archives of dermatological research · 2023Article
- Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.bioRxiv : the preprint server for biology · 2023Article
- CIRP attenuates acute kidney injury after hypothermic cardiovascular surgery by inhibiting PHD3/HIF-1α-mediated ROS-TGF-β1/p38 MAPK activation and mitochondrial apoptotic pathways.Molecular medicine (Cambridge, Mass.) · 2023Article
- miR-210 Expression Is Strongly Hypoxia-Induced in Anaplastic Thyroid Cancer Cell Lines and Is Associated with Extracellular Vesicles and Argonaute-2.International journal of molecular sciences · 2023Article
- The transition from HIF-1 to HIF-2 during prolonged hypoxia results from reactivation of PHDs and HIF1A mRNA instability.Cellular & molecular biology letters · 2022Article
- The human blood transcriptome exhibits time-of-day-dependent response to hypoxia: Lessons from the highest city in the world.Cell reports · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial cells (ECs) are the primary sensors of variations in blood oxygen concentrations. They use the hypoxia-sensitive stabilization of the hypoxia-inducible factor-1α (HIF-1α) transcription factor to engage specific transcriptional programs in response to oxygen changes. The regulation of HIF-1α expression is well documented at the protein level, but much less is known about the control of its mRNA stability. Using small interfering RNA knockdown experiments, reporter gene analyses, ribonucleoprotein immunoprecipitations, and mRNA half-life determinations, we report a new regulatory mechanism of HIF-1α expression in ECs. We demonstrate that 1) sustained hypoxia progressively decreases HIF-1α mRNA while HIF-1α protein levels rapidly peak after 3 h and then slowly decay; 2) silencing the mRNA-destabilizing protein tristetraprolin (TTP) in ECs reverses hypoxia-induced down-regulation of HIF-1α mRNA; 3) the decrease in the half-life of Luciferase-HIF-1α-3'UTR reporter transcript that is observed after prolonged hypoxia is mediated by TTP; 4) TTP binds specifically to HIF-1α 3'UTR; and 5) the most distal AU-rich elements present in HIF-1α 3'UTR (composed of two hexamers) are sufficient for TTP-mediated repression. Finally, we bring evidence that silencing TTP expression enhances hypoxia-induced increase in HIF-1α protein levels with a concomitant increase in the levels of the carbonic anhydrase enzyme CA IX, thus suggesting that TTP physiologically controls the expression of a panel of HIF-1α target genes. Altogether, these data reveal a new role for TTP in the control of gene expression during the response of endothelial cell to hypoxia.
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Registered trials
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