ArticleProceedings of the National Academy of Sciences of the United States of America2000
Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
254 citing papers in PubMed, 1 synthesis or guideline pooled it, 649 citations in OpenAlex.
- Clinicopathological significance of hypoxia-inducible factor-1 alpha polymorphisms in cancers: evidence from a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Pooled it
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Large-scale quaternary structural transitions underlie gain of function of SPOP cancer mutations.Molecular cell · 2026Article
- Natural Phytochemicals as Inhibitors of HIF-1α in Breast Cancer: Review of Preclinical Evidence and Future Prospects.Current issues in molecular biology · 2026Review
- Immunomodulatory and anti-inflammatory potential of S-nitrosoglutathione (GSNO) in multiple sclerosis: a review of mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- pVHL regulates protein stability of the TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation.Cellular and molecular life sciences : CMLS · 2025Article
- A Functional Assay for Mining Noninhibitory Enzyme Ligands from One Bead One Compound Libraries: Application to E3 Ubiquitin Ligases.Journal of the American Chemical Society · 2025Article
- ELOC-Mutated Renal Cell Carcinoma is a Rare Indolent Tumor With Distinctive Genomic Characteristics.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- The equilibrium between two quaternary assembly states determines the activity of SPOP and its cancer mutants.bioRxiv : the preprint server for biology · 2025Article
- Genome-wide identification of socs gene in rainbow trout (Oncorhynchus mykiss) and response to microplastic exposure.Molecular biology reports · 2025Article
- Discovery of a Series of Covalent Ligands That Bind to Cys77 of the Von Hippel-Lindau Tumor Suppressor Protein (VHL).ACS medicinal chemistry letters · 2025Article
- A Boolean network model of hypoxia, mechanosensing and TGF-β signaling captures the role of phenotypic plasticity and mutations in tumor metastasis.PLoS computational biology · 2025Article
- Hypoxia-inducible factor 1α is required to establish the larval glycolytic program in Drosophila melanogaster.Molecular metabolism · 2025Article
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- Hypoxia-inducible factor 1α is required to establish the larval glycolytic program inbioRxiv : the preprint server for biology · 2025Article
- A closer look at the role of deubiquitinating enzymes in the Hypoxia Inducible Factor pathway.Biochemical Society transactions · 2024Review
- Time-resolved NMR detection of prolyl-hydroxylation in intrinsically disordered region of HIF-1α.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hypoxia-inducible factor-driven glycolytic adaptations in host-microbe interactions.Pflugers Archiv : European journal of physiology · 2024Review
- The Role of the PAX Genes in Renal Cell Carcinoma.International journal of molecular sciences · 2024Review
194 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the VHL tumor suppressor gene result in constitutive expression of many hypoxia-inducible genes, at least in part because of increases in the cellular level of hypoxia-inducible transcription factor HIF1alpha, which in normal cells is rapidly ubiquitinated and degraded by the proteasome under normoxic conditions. The recent observation that the VHL protein is a subunit of an Skp1-Cul1/Cdc53-F-box (SCF)-like E3 ubiquitin ligase raised the possibility that VHL may be directly responsible for regulating cellular levels of HIF1alpha by targeting it for ubiquitination and proteolysis. In this report, we test this hypothesis directly. We report development of methods for production of the purified recombinant VHL complex and present direct biochemical evidence that it can function with an E1 ubiquitin-activating enzyme and E2 ubiquitin-conjugating enzyme to activate HIF1alpha ubiquitination in vitro. Our findings provide new insight into the function of the VHL tumor suppressor protein, and they provide a foundation for future investigations of the mechanisms underlying VHL regulation of oxygen-dependent gene expression.
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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.