ArticleThe Journal of biological chemistry2006
Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 110 citations in OpenAlex.
- Hypoxic microenvironment in cancer: role in metabolic reprogramming.Frontiers in oncology · 2026Review
- The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting.Frontiers in cell and developmental biology · 2023Review
- Gene regulation by histone-modifying enzymes under hypoxic conditions: a focus on histone methylation and acetylation.Experimental & molecular medicine · 2022Review
- Stanniocalcin 2 (STC2): a universal tumour biomarker and a potential therapeutical target.Journal of experimental & clinical cancer research : CR · 2022Review
- HIF‑1α in cerebral ischemia (Review).Molecular medicine reports · 2022Review
- Characterization of the MYB-inhibitory potential of the Pan-HDAC inhibitor LAQ824.BBA advances · 2022Article
- Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis.International journal of molecular sciences · 2021Review
- Review
- Phase I study of the mTOR inhibitor everolimus in combination with the histone deacetylase inhibitor panobinostat in patients with advanced clear cell renal cell carcinoma.Investigational new drugs · 2020Article
- Phase I studies of vorinostat with ixazomib or pazopanib imply a role of antiangiogenesis-based therapy for TP53 mutant malignancies.Scientific reports · 2020Article
- HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice.Theranostics · 2020Article
- Review
- Targeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy.Nutrients · 2018Review
- The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia.Nucleic acids research · 2018Article
- Histone Deacetylase Inhibitors Protect Against Pyruvate Dehydrogenase Dysfunction in Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- HDAC6 regulates sensitivity to cell death in response to stress and post-stress recovery.Cell stress & chaperones · 2017Article
- Review
- Class I and IIa HDACs Mediate HIF-1α Stability Through PHD2-Dependent Mechanism, While HDAC6, a Class IIb Member, Promotes HIF-1α Transcriptional Activity in Nucleus Pulposus Cells of the Intervertebral Disc.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of Stressed Cells.Journal of cellular biochemistry · 2016Review
- Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors regulating the oxygen supply, glucose metabolism, and angiogenesis. HIF function requires the recruitment of p300/CREB-binding protein, two coactivators with histone acetyltransferase activity, by the C-terminal transactivation domain of HIF-alpha (HIF-alphaCAD). Histone deacetylase inhibitors (HDAIs) induce differentiation or apoptosis and repress tumor growth and angiogenesis, hence being explored intensively as anti-cancer agents. Using combined pharmacological, biochemical, and genetic approaches, here we show that HDAIs repress the transactivation potential of HIF-alphaCAD. This repression is independent of the function of tumor suppressors von Hippel-Lindau or p53 or the degradation of HIF-alpha. We also demonstrate the sufficiency of low concentrations of HDAIs in repression of HIF target genes in tumor cells. We further show that HDAIs induce hyperacetylation of p300 and repress the HIF-1alpha.p300 complex in vivo. In vitro acetylation analysis reveals that the p300CH1 region, but not HIF-alphaCAD, is susceptible to acetylation. Taken together, our data demonstrate that a deacetylase activity is indispensable for the transactivation potential of HIF-alphaCAD and support a model that acetylation regulates HIF function by targeting HIF-alpha.p300 complex, not by direct acetylating HIF-alpha. The demonstration that HDAIs repress both HIF-1alpha and HIF-2alpha transactivation potential independently of von Hippel-Lindau tumor suppressor and p53 function indicates that HDAIs may have biological effects in a broad range of tissues in addition to tumors.
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Registered trials
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.