ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
von Hippel-Lindau-dependent patterns of RNA polymerase II hydroxylation in human renal clear cell carcinomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- Survival Prediction for Postoperative Patients With Kidney Cancer Based on Computed Tomography Radiomics: Retrospective Cohort Study.JMIR medical informatics · 2025Article
- Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.Molecular neurobiology · 2024Review
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma.Frontiers in genetics · 2022Article
- Tobacco smoking induces metabolic reprogramming of renal cell carcinoma.The Journal of clinical investigation · 2021Article
- Interaction with p53 explains a pro-proliferative function for VHL in cancer.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Prolyl Hydroxylase Domain-2 Protein Regulates Lipopolysaccharide-Induced Vascular Inflammation.The American journal of pathology · 2019Article
- The PHD1 oxygen sensor in health and disease.The Journal of physiology · 2018Review
- VHL missense mutations in the p53 binding domain show different effects on p53 signaling and HIFα degradation in clear cell renal cell carcinoma.Oncotarget · 2017Article
- Article
- PHD2: from hypoxia regulation to disease progression.Hypoxia (Auckland, N.Z.) · 2016Review
- TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma.Cancer cell · 2014Article
- Polymorphism in PHD1 gene and risk of non-small cell lung cancer in a Chinese population.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Krüppel-like factor 8 contributes to hypoxia-induced MDR in gastric cancer cells.Cancer science · 2014Article
- The role of HIF1α in renal cell carcinoma tumorigenesis.Journal of molecular medicine (Berlin, Germany) · 2014Review
- Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism.Hypoxia (Auckland, N.Z.) · 2014Review
- Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.PloS one · 2013Article
- VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma.Cancer cell · 2012Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeWe have previously shown that von Hippel-Lindau (VHL) regulates ubiquitylation and proline 1465 hydroxylation of the large subunit of RNA polymerase II, Rpb1, in human renal clear cell carcinoma (RCC) cell lines. Here, our goal was to determine the effect of this VHL function and the status of P1465 hydroxylation in human RCC tumors. EXPERIMENTAL
designPrimary human tumors and matched normal kidney samples were probed for expression levels of the large subunit of RNA polymerase II (Rpb1), Rpb1 hydroxylated on P1465 [Rpb1(OH)], Rpb1 phosphorylated on Ser5 [Rpb1(S5P)], and proline hydroxylases PHD1, PHD2, and PHD3. Results from RCC tumors were categorized according to the status of VHL gene. Mechanistic analysis was performed in orthotopic xenograft model using 786-O RCC cells with wild-type (WT) VHL and knockdown of PHD2, characterized by high levels of Rpb1(OH) and PHD1.
resultsLevels of Rpb1(OH), PHD1, and PHD2 were significantly higher in RCC tumors compared with normal kidneys. RCC tumors with WT VHL had higher levels of Rpb1(OH) and PHD1 and lower levels of PHD2 than tumors with VHL gene alterations. Levels of Rpb1(OH) significantly correlated with levels of PHD1 in tumors and normal kidneys. Knockdown of PHD2 in 786-O VHL(+) cells resulted in a more malignant phenotype in orthotopic xenografts and higher expression of specific cell cycle regulators (CDC25A, cyclin-dependent kinase 2, CCNA2) compared with VHL(-) RCC cells.
conclusionsElevated PHD1 concomitant with decreased PHD2 are causatively related to Rpb1 hydroxylation and oncogenesis in human RCC tumors with WT VHL gene. Thus, P1465-hydroxylated Rpb1 and PHD1 represent attractive drug targets for new RCC treatments.
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