ArticleMolecular and cellular biology1997
The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 342 citations in OpenAlex.
- A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer.The New England journal of medicine · 2003Trial
- Unraveling the role of specificity protein 1 in gliomas: pathophysiology and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The role of Cannabidiol and tetrahydrocannabivarin to overcome doxorubicin resistance in MDA-MB-231 xenografts in athymic nude mice.Biochimie · 2023Article
- Licochalcone A Suppresses Renal Cancer Cell Proliferation and Metastasis by Engagement of Sp1-Mediated LC3 Expression.Pharmaceutics · 2023Article
- Prognostic and predictive significance of VEGF, CD31, and Ang-1 in patients with metastatic clear cell renal cell carcinoma treated with first-line sunitinib.Biomolecules & biomedicine · 2023Article
- VHL tumor suppressor as a novel potential candidate biomarker in papillary thyroid carcinoma.Biomolecules & biomedicine · 2023Review
- Adenosine, bridging chronic inflammation and tumor growth.Frontiers in immunology · 2023Review
- Interaction with p53 explains a pro-proliferative function for VHL in cancer.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Synchronous inhibition of mTOR and VEGF/NRP1 axis impedes tumor growth and metastasis in renal cancer.NPJ precision oncology · 2019Article
- Suppression of glioblastoma growth and angiogenesis through molecular targeting of methionine aminopeptidase-2.Journal of neuro-oncology · 2018Article
- The hypoxia-adenosine link during inflammation.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Review
- Deletion of endothelial cell-specific liver kinase B1 increases angiogenesis and tumor growth via vascular endothelial growth factor.Oncogene · 2017Article
- VHL deficiency augments anthracycline sensitivity of clear cell renal cell carcinomas by down-regulating ALDH2.Nature communications · 2017Article
- Single-stage laparoscopic adrenalectomy for pheochromocytoma and enucleation of a pancreatic neuroendocrine tumor in Von Hippel-Lindau disease: A case report.Molecular and clinical oncology · 2017Article
- Genome-wide mapping of Hif-1α binding sites in zebrafish.BMC genomics · 2015Article
- Corticotropin Releasing Hormone and Urocortin 3 Stimulate Vascular Endothelial Growth Factor Expression through the cAMP/CREB Pathway.The Journal of biological chemistry · 2015Article
- Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo.Scientific reports · 2015Article
- ZBRK1, a novel tumor suppressor, activates VHL gene transcription through formation of a complex with VHL and p300 in renal cancer.Oncotarget · 2015Article
- VHL, the story of a tumour suppressor gene.Nature reviews. Cancer · 2015Review
- KLF4 Promotes Angiogenesis by Activating VEGF Signaling in Human Retinal Microvascular Endothelial Cells.PloS one · 2015Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The von Hippel-Lindau tumor suppressor gene (VHL) has a critical role in the pathogenesis of clear-cell renal cell carcinoma (RCC), as VHL mutations have been found in both von Hippel-Lindau disease-associated and sporadic RCCs. Recent studies suggest that vascular endothelial growth factor (VEGF) mRNA is upregulated in RCC- and von Hippel-Lindau disease-associated tumors. We have therefore assessed the effect of the VHL gene product on VEGF expression. VEGF promoter-luciferase constructs were transiently cotransfected with a wild-type VHL (wt-VHL) vector in several cell lines, including 293 embryonic kidney and RCC cell lines. wt-VHL protein inhibited VEGF promoter activity in a dose-dependent manner up to 5- to 10-fold. Deletion analysis defined a 144-bp region of the VEGF promoter necessary for VHL repression. This VHL-responsive element is GC rich and specifically binds the transcription factor Sp1 in crude nuclear extracts. In Drosophila cells, cotransfected VHL represses Sp1-mediated activation but not basal activity of the VEGF promoter. We next demonstrated in coimmunoprecipitates that VHL and Sp1 were part of the same complex and, by using a glutathione-S-transferase-VHL fusion protein and purified Sp1, that VHL and Sp1 directly interact. Furthermore, endogenous VEGF mRNA levels were suppressed in permanent RCC cell lines expressing wt-VHL, and nuclear run-on studies indicated that VHL regulation of VEGF occurs at least partly at the transcriptional level. These observations support a new mechanism for VHL-mediated transcriptional repression via a direct inhibitory action on Sp1 and suggest that loss of Sp1 inhibition may be important in the pathogenesis of von Hippel-Lindau disease and RCC.
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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.