ArticleExperimental & molecular medicine2008
STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination.
Article in Experimental & molecular medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 119 citations in OpenAlex.
- Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome.The Journal of clinical investigation · 2020Trial
- Astrocyte-derived IL-17A facilitates angiogenesis following ischemia-like injury via an IL-6-dependent STAT3-VEGF signaling cascade.Behavioral and brain functions : BBF · 2026Article
- Genome-wide CRISPR screen identifies a cytokine-enhancer circuit driving HIF-2α activation in renal cancer.The Journal of clinical investigation · 2026Article
- Signal Transducer and Activator of Transcription (STAT) Proteins Regulate Mucosal-Associated Invariant T (MAIT) Cell Function.Immunology · 2026Article
- Hypoxia regulates Th17/Treg balance by altering chromatin accessibility and gene expression.The FEBS journal · 2026Article
- Network Pharmacology & Validation of Dihydrotanshinone I's Regulation of HIF-1α via STAT3 in Cardiomyocytes.Acta Cardiologica Sinica · 2026Article
- HIF-1α: a bridge connecting sepsis and acute respiratory distress syndrome.European journal of medical research · 2025Review
- Oxygen Sensing in Osteocytes: From Physiology to Age-related Osteoporosis.Current osteoporosis reports · 2025Review
- Loss of TC-PTP in keratinocytes leads to increased UVB-induced autophagy.Cell death discovery · 2025Article
- Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells.International journal of molecular sciences · 2025Article
- Qi-Gui-Sheng-Jiang-San Decoction Regulating Hypoxia Response Through Non-Oxygen-Dependent Pathway Improves Diabetic Kidney Disease: Coupling Network Pharmacology With Experimental Verification.Journal of diabetes research · 2025Article
- Emerging Therapeutic Targets in Rheumatoid Arthritis: Focusing on HIF-1α, Nrf2, STATs, and RORγt.Current drug targets · 2025Review
- Unraveling the role of STAT3 in Cancer Cachexia: pathogenic mechanisms and therapeutic opportunities.Frontiers in endocrinology · 2025Review
- Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors.Frontiers in cell and developmental biology · 2025Review
- Inhibition of STAT3 by 2-Methoxyestradiol suppresses M2 polarization and protumoral functions of macrophages in breast cancer.BMC cancer · 2024Article
- Review
- Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia.Cell death discovery · 2023Article
- Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance.International journal of molecular sciences · 2023Review
- A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors.Open medicine (Warsaw, Poland) · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor 1alpha (HIF-1alpha) is rapidly degraded by the ubiquitin-proteasome pathway under normoxic conditions. Ubiquitination of HIF-1alpha is mediated by interaction with von Hippel-Lindau tumor suppressor protein (pVHL). In our previous report, we found that hypoxia-induced active signal transducer and activator of transcription3 (STAT3) accelerated the accumulation of HIF-1alpha protein and prolonged its half-life in solid tumor cells. However, its specific mechanisms are not fully understood. Thus, we examined the role of STAT3 in the mechanism of pVHL-mediated HIF-1alpha stability. We found that STAT3 interacts with C-terminal domain of HIF-1alpha and stabilizes HIF-1alpha by inhibition of pVHL binding to HIF-1alpha. The binding between HIF-1alpha and pVHL, negative regulator of HIF-1alpha stability, was interfered dose-dependently by overexpressed constitutive active STAT3. Moreover, we found that the enhanced HIF-1alpha protein levels by active STAT3 are due to decrease of poly-ubiquitination of HIF-1alpha protein via inhibition of interaction between pVHL and HIF-1alpha. Taken together, our results suggest that STAT3 decreases the pVHL-mediated ubiquitination of HIF-1alpha through competition with pVHL for binding to HIF-1 alpha, and then stabilizes HIF-1alpha protein levels.
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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.