ArticleScience signaling2016
Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1.
Article in Science signaling, 2016. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 114 citations in OpenAlex.
- Article
- Chronic stress and cancer progression through neuro‑endocrine‑immune networks (Review).Oncology reports · 2026Review
- Deciphering the interplay between hypoxia, angiogenesis, and endoplasmic reticulum stress in carcinogenesis: A narrative review.World journal of experimental medicine · 2026Review
- EGLN1 (PHD2) role in tumor microenvironment: insights for therapeutic targeting.Experimental & molecular medicine · 2025Review
- Excessive HIF-1α driven by phospholipid metabolism causes septic cardiomyopathy through cytopathic hypoxia.Nature cardiovascular research · 2025Article
- Linking phospholipid metabolism to septic cardiomyopathy via HIF-1α overactivation.Nature cardiovascular research · 2025Article
- Oxygen-carrying nanoemulsions and respiratory hyperoxia eliminate tumor hypoxia-induced immunosuppression.JCI insight · 2025Article
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects.Cellular and molecular life sciences : CMLS · 2025Review
- rBCG-LTAK63 enhances protection against tuberculosis by inducing autophagy and circadian gene regulation.Frontiers in immunology · 2025Article
- Adrenal epinephrine facilitates erythropoietin gene activation by hypoxia through β2 adrenergic receptor interaction with Hif-2α.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.Genes & diseases · 2024Article
- Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.Molecular neurobiology · 2024Review
- Investigation of Glycosylphosphatidylinositol (GPI)-Plasma Membrane Interaction in Live Cells and the Influence of GPI Glycan Structure on the Interaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Combinatorial regulation by ERK1/2 and CK1δ protein kinases leads to HIF-1α association with microtubules and facilitates its symmetrical distribution during mitosis.Cellular and molecular life sciences : CMLS · 2024Article
- 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
- Tongmai Yangxin pill alleviates myocardial no-reflow by activating GPER to regulate HIF-1α signaling and downstream potassium channels.Pharmaceutical biology · 2023Article
- A2AR Expression and Immunosuppressive Environment Independent ofBiomedicines · 2023Article
- The interplay between the DNA damage response and ectonucleotidases modulates tumor response to therapy.Science immunology · 2023Review
- Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes encoding proteins that enable cells to adapt to reduced O2 availability. Proteins encoded by HIF-1 target genes play a central role in mediating physiological processes that are dysregulated in cancer and heart disease. These diseases are also characterized by increased production of cyclic adenosine monophosphate (cAMP), the allosteric activator of cAMP-dependent protein kinase A (PKA). Using glutathione S-transferase pull-down, coimmunoprecipitation, and mass spectrometry analyses, we demonstrated that PKA interacts with HIF-1α in HeLa cervical carcinoma cells and rat cardiomyocytes. PKA phosphorylated Thr(63) and Ser(692) on HIF-1α in vitro and enhanced HIF transcriptional activity and target gene expression in HeLa cells and rat cardiomyocytes. PKA inhibited the proteasomal degradation of HIF-1α in an O2-independent manner that required the phosphorylation of Thr(63) and Ser(692) and was not affected by prolyl hydroxylation. PKA also stimulated the binding of the coactivator p300 to HIF-1α to enhance its transcriptional activity and counteracted the inhibitory effect of asparaginyl hydroxylation on the association of p300 with HIF-1α. Furthermore, increased cAMP concentrations enhanced the expression of HIF target genes encoding CD39 and CD73, which are enzymes that convert extracellular adenosine 5'-triphosphate to adenosine, a molecule that enhances tumor immunosuppression and reduces heart rate and contractility. These data link stimuli that promote cAMP signaling, HIF-1α-dependent changes in gene expression, and increased adenosine, all of which contribute to the pathophysiology of cancer and heart disease.
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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.