ArticleCell reports2013
Proteostasis modulators prolong missense VHL protein activity and halt tumor progression.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease.Journal of neurosurgery · 2014Trial
- The VHL tumor suppressor at the crossroad of protein folding, aggregation, and cancer.Molecular oncology · 2026Review
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- Targeting chaperone modifications: Innovative approaches to cancer treatment.The Journal of biological chemistry · 2024Review
- Spinal cord hemangioblastomas in von Hippel-Lindau disease.Neuro-oncology advances · 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
- Proteostasis Modulation in Germline Missense von Hippel Lindau Disease.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- How to fix a broken protein: restoring function to mutant human cystathionine β-synthase.Human genetics · 2022Review
- Genetic Counseling and Long-Term Surveillance Using a Multidisciplinary Approach in von Hippel-Lindau Disease.Annals of laboratory medicine · 2022Article
- Clinical characteristics, surgical management, and prognostic factors for supratentorial hemangioblastoma: A retrospective study.Frontiers in surgery · 2022Article
- Claudin-10 overexpression suppresses human clear cell renal cell carcinoma growth and metastasis by regulating ATP5O and causing mitochondrial dysfunction.International journal of biological sciences · 2022Article
- Understanding the Origins of Loss of Protein Function by Analyzing the Effects of Thousands of Variants on Activity and Abundance.Molecular biology and evolution · 2021Article
- Folliculin variants linked to Birt-Hogg-Dubé syndrome are targeted for proteasomal degradation.PLoS genetics · 2020Article
- The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation.PLoS genetics · 2020Article
- mTORC2/Rac1 Pathway Predisposes Cancer Aggressiveness inCancers · 2020Article
- Repurposing propranolol as an antitumor agent in von Hippel-Lindau disease.Journal of neurosurgery · 2019Article
- Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors.PLoS computational biology · 2019Article
- miR-31-5p Is a LIPUS-Mechanosensitive MicroRNA that Targets HIF-1α Signaling and Cytoskeletal Proteins.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Although missense mutations of the von Hippel-Lindau disease (VHL) gene are the most common germline mutation underlying this heritable cancer syndrome, the mechanism of tumorigenesis is unknown. We found a quantitative reduction of missense mutant VHL protein (pVHL) in tumors associated with physiologic mRNA expression. Although mutant pVHL is unstable and degraded contemporarily with translation, it retains its E3 ligase function, including hypoxia-inducible factor degradation. The premature pVHL degradation is due to misfolding and imbalance of chaperonin binding. Histone deacetylase inhibitors (HDACIs) can modulate this pathway by inhibiting the HDAC-Hsp90 chaperone axis, stabilizing pVHL, and restoring activity comparable to wild-type protein, both in vitro and in animal models. Furthermore, HDACI-mediated stabilization of missense pVHL significantly attenuates the growth of 786-O rodent tumor model. These findings provide direct biological insight into VHL-associated tumors and elucidate a treatment paradigm for VHL.
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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.