ArticleCell cycle (Georgetown, Tex.)2015
AMPK-HDAC5 pathway facilitates nuclear accumulation of HIF-1α and functional activation of HIF-1 by deacetylating Hsp70 in the cytosol.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 121 citations in OpenAlex.
- Targeting Microglial HDAC5 Suppresses NLRP3 Inflammation via NF-κB Deacetylation to Alleviate Ischemic Brain Injury.CNS neuroscience & therapeutics · 2026Article
- Vitamin D and hypoxia-inducible factors signaling interplay: A hypothesis-driven review of therapeutic strategies for acute cerebral infarction.Metabolic brain disease · 2026Review
- Hypoxia, ROS, and HIF Signaling in I/R Injury: Implications and Future Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Potential roles of histone deacetylases in diabetic wound healing.World journal of diabetes · 2025Review
- The Value of Electroacupuncture in the Treatment of Coronary Heart Disease: A Review of the Mechanisms and Clinical Studies of Electroacupuncture Therapy.Cardiology research and practice · 2025Review
- Mechanisms and therapeutic prospects of hypoxia-inducible factor 1-alpha in acute kidney injury: a systematic review.Frontiers in cell and developmental biology · 2025Review
- Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025Review
- Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia.Journal of translational medicine · 2024Article
- Polydatin inhibits histone deacetylase 1 and shows an anti-angiogenic action in head and neck squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2024Article
- Article
- Dysregulation of histone deacetylases in ocular diseases.Archives of pharmacal research · 2024Review
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
- AMPK-HIF-1α signaling enhances glucose-derived de novo serine biosynthesis to promote glioblastoma growth.Journal of experimental & clinical cancer research : CR · 2023Article
- Targeting histone deacetylases for cancer therapy: Trends and challenges.Acta pharmaceutica Sinica. B · 2023Review
- WSSV exploits AMPK to activate mTORC2 signaling for proliferation by enhancing aerobic glycolysis.Communications biology · 2023Article
- HIF: a master regulator of nutrient availability and metabolic cross-talk in the tumor microenvironment.The EMBO journal · 2023Review
- FGF2 Alleviates Microvascular Ischemia-Reperfusion Injury by KLF2-mediated Ferroptosis Inhibition and Antioxidant Responses.International journal of biological sciences · 2023Article
- Suberoylanilide hydroxamic acid suppresses axonal damage and neurological dysfunction after subarachnoid hemorrhage via the HDAC1/HSP70/TDP-43 axis.Experimental & molecular medicine · 2022Article
- Human milk oligosaccharide 2'-fucosyllactose promotes melanin degradation via the autophagic AMPK-ULK1 signaling axis.Scientific reports · 2022Article
- Gene regulation by histone-modifying enzymes under hypoxic conditions: a focus on histone methylation and acetylation.Experimental & molecular medicine · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor 1 (HIF-1) transcriptionally promotes production of adenosine triphosphate (ATP) whereas AMPK senses and regulates cellular energy homeostasis. A histone deacetylase (HDAC) activity has been proven to be critical for HIF-1 activation but the underlying mechanism and its role in energy homesostasis remain unclear. Here, we demonstrate that HIF-1 activation depends on a cytosolic, enzymatically active HDAC5. HDAC5 knockdown impairs hypoxia-induced HIF-1α accumulation and HIF-1 transactivation, whereas HDAC5 overexpression enhances HIF-1α stabilization and nuclear translocation. Mechanistically, we show that Hsp70 is a cytosolic substrate of HDAC5; and hyperacetylation renders Hsp70 higher affinity for HIF-1α binding, which correlates with accelerated degradation and attenuated nuclear accumulation of HIF-1α. Physiologically, AMPK-triggered cytosolic shuttling of HDAC5 is critical; inhibition of either AMPK or HDAC5 impairs HIF-1α nuclear accumulation under hypoxia or low glucose conditions. Finally, we show specifically suppressing HDAC5 is sufficient to inhibit tumor cell proliferation under hypoxic conditions. Our data delineate a novel link between AMPK, the energy sensor, and HIF-1, the major driver of ATP production, indicating that specifically inhibiting HDAC5 may selectively suppress the survival and proliferation of hypoxic tumor cells.
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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.