ArticleJournal of biomolecular screening2012
Agents that stabilize mutated von Hippel-Lindau (VHL) protein: results of a high-throughput screen to identify compounds that modulate VHL proteostasis.
Article in Journal of biomolecular screening, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- VHL-P138R and VHL-L163R Novel Variants: Mechanisms of VHL Pathogenicity Involving HIF-Dependent and HIF-Independent Actions.Frontiers in endocrinology · 2022Article
- Clear cell renal cell carcinoma ontogeny and mechanisms of lethality.Nature reviews. Nephrology · 2021Review
- Identification of 8-Azaguanine Biosynthesis-Related Genes Provides Insight Into the Enzymatic and Non-enzymatic Biosynthetic Pathway for 1,2,3-Triazole.Frontiers in bioengineering and biotechnology · 2020Article
- Arginine refolds, stabilizes, and restores function of mutant pVHL proteins in animal model of the VHL cancer syndrome.Oncogene · 2019Article
- Phosphorylation-dependent cleavage regulates von Hippel Lindau proteostasis and function.Oncogene · 2016Article
- Targeting tumor suppressor genes for cancer therapy.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Review
- The PI3K/AKT Pathway and Renal Cell Carcinoma.Journal of genetics and genomics = Yi chuan xue bao · 2015Review
- Article
- VHL, the story of a tumour suppressor gene.Nature reviews. Cancer · 2015Review
- Genetic and pharmacological strategies to refunctionalize the von Hippel Lindau R167Q mutant protein.Cancer research · 2014Article
- Characterization of novel inhibitors of HIV-1 replication that function via alteration of viral RNA processing and rev function.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that affects multiple organs. Treatment is mainly surgical, and effective systemic therapies are needed. We developed a cell-based screening tool to identify compounds that stabilize or upregulate full-length, point-mutated VHL protein. The 786-0 cell line was infected with full-length W117A-mutated VHL linked to a C-terminal Venus fluorescent protein. This VHL-W117A-Venus line was used to screen the Prestwick drug library and was tested against proteasome inhibitors MG132 and bortezomib. Western blot validation and evaluation of functional readouts, including hypoxia-inducible factor 2α (HIF2α) and glucose transporter 1 (Glut1) levels, were performed. We found that bortezomib, MG132, and the Prestwick compounds 8-azaguanine, thiostrepton, and thioguanosine upregulated VHL-W117A-Venus in 786-0 cells. 8-Azaguanine downregulated HIF2α levels and was augmented by the presence of VHL W117A. VHL p30 band intensities varied as a function of compound used, suggesting alternate posttranslational processing. Nuclear-cytoplasmic localization of VHL-W117A-Venus varied among the different compounds. In conclusion, a 786-0 cell line containing VHL-W117A-Venus was successfully used to identify compounds that upregulate VHL levels, with differential effect on VHL intracellular localization and posttranslational processing. Further screening efforts will broaden the number of pharmacophores available to develop therapeutic agents that will upregulate and refunctionalize mutated VHL.
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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.