ArticleOncogene2009
The von Hippel-Lindau protein sensitizes renal carcinoma cells to apoptotic stimuli through stabilization of BIM(EL).
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- SNAI2-Mediated Repression ofCancer research · 2021Article
- MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim.Molecular medicine reports · 2020Article
- pVHL-mediated regulation of the anti-angiogenic protein thrombospondin-1 decreases migration of Clear Cell Renal Carcinoma Cell Lines.Scientific reports · 2020Article
- EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Adenoviral delivery of VHL suppresses bone sarcoma cell growth through inhibition of Wnt/β-catenin signaling.Cancer gene therapy · 2019Article
- Arginine refolds, stabilizes, and restores function of mutant pVHL proteins in animal model of the VHL cancer syndrome.Oncogene · 2019Article
- VHL promotes immune response against renal cell carcinoma via NF-κB-dependent regulation of VCAM-1.The Journal of cell biology · 2017Article
- Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Low VHL mRNA expression is associated with more aggressive tumor features of papillary thyroid carcinoma.PloS one · 2014Article
- Complex cellular functions of the von Hippel-Lindau tumor suppressor gene: insights from model organisms.Oncogene · 2012Review
- pVHL-mediated transcriptional repression of c-Myc by recruitment of histone deacetylases.Molecules and cells · 2012Article
- Loss of the Birt-Hogg-Dubé tumor suppressor results in apoptotic resistance due to aberrant TGFβ-mediated transcription.Oncogene · 2011Article
- YueF overexpression inhibits cell proliferation partly through p21 upregulation in renal cell carcinoma.International journal of molecular sciences · 2011Article
- Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth.International journal of cancer · 2010Article
- Von Hippel-Lindau syndrome: molecular mechanisms of the disease.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2010Review
- Bim upregulation by histone deacetylase inhibitors mediates interactions with the Bcl-2 antagonist ABT-737: evidence for distinct roles for Bcl-2, Bcl-xL, and Mcl-1.Molecular and cellular biology · 2009Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
von Hippel-Lindau (VHL) disease is caused by germ-line mutations in the VHL tumor suppressor gene and is the most common cause of inherited renal cell carcinoma (RCC). Mutations in the VHL gene also occur in a large majority of sporadic cases of clear-cell RCC, which have high intrinsic resistance to chemotherapy and radiotherapy. Here we show that VHL-deficient RCC cells express lower levels of the proapoptotic Bcl-2 family protein BIM(EL) and are more resistant to etoposide and UV radiation-induced death compared to the same cells stably expressing the wild-type VHL protein (pVHL). Reintroducing pVHL into VHL-null cells increased the half-life of BIM(EL) protein without affecting its mRNA expression, and overexpressing pVHL inhibited BIM(EL) polyubiquitination. Suppressing pVHL expression with RNA interference resulted in a decrease in BIM(EL) protein and a corresponding decrease in the sensitivity of RCC cells to apoptotic stimuli. Directly inhibiting BIM(EL) expression in pVHL-expressing RCC cells caused a similar decrease in cell death. These results demonstrate that pVHL acts to promote BIM(EL) protein stability in RCC cells, and that destabilization of BIM(EL) in the absence of pVHL contributes to the increased resistance of VHL-null RCC cells to certain apoptotic stimuli.
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