ArticleMolecular and cellular biology2008
The von Hippel-Lindau tumor suppressor protein and Egl-9-Type proline hydroxylases regulate the large subunit of RNA polymerase II in response to oxidative stress.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 119 citations in OpenAlex.
- Comparison of Histone H3K4me3 between IVF and ICSI Technologies and between Boy and Girl Offspring.International journal of molecular sciences · 2021Trial
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.Scientific reports · 2024Article
- Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.Molecular neurobiology · 2024Review
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.bioRxiv : the preprint server for biology · 2024Article
- HypDB: A functionally annotated web-based database of the proline hydroxylation proteome.PLoS biology · 2022Article
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- Article
- Review
- Association of Oxidative Stress with Neurological Disorders.Current neuropharmacology · 2022Article
- Oxidative stress induces Ser 2 dephosphorylation of the RNA polymerase II CTD and premature transcription termination.Transcription · 2021Article
- Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer.Oncogene · 2021Review
- Epigenetic regulators of neuronal ferroptosis identify novel therapeutics for neurological diseases: HDACs, transglutaminases, and HIF prolyl hydroxylases.Neurobiology of disease · 2021Review
- The mProceedings of the National Academy of Sciences of the United States of America · 2020Article
- The pVHL neglected functions, a tale of hypoxia-dependent and -independent regulations in cancer.Open biology · 2020Review
- A combinatorial view of old and new RNA polymerase II modifications.Transcription · 2020Review
- Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates.eLife · 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
- Bexarotene - a novel modulator of AURKA and the primary cilium inJournal of cell science · 2018Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Human renal clear cell carcinoma (RCC) is frequently associated with loss of the von Hippel-Lindau (VHL) tumor suppressor (pVHL), which inhibits ubiquitylation and degradation of the alpha subunits of hypoxia-inducible transcription factor. pVHL also ubiquitylates the large subunit of RNA polymerase II, Rpb1, phosphorylated on serine 5 (Ser5) within the C-terminal domain (CTD). A hydroxylated proline 1465 within an LXXLAP motif located N-terminal to the CTD allows the interaction of Rpb1 with pVHL. Here we report that in RCC cells, pVHL regulates expression of Rpb1 and is necessary for low-grade oxidative-stress-induced recruitment of Rpb1 to the DNA-engaged fraction and for its P1465 hydroxylation, phosphorylation, and nondegradative ubiquitylation. Egln-9-type prolyl hydroxylases, PHD1 and PHD2, coimmunoprecipitated with Rpb1 in the chromatin fraction of VHL(+) RCC cells in response to oxidative stress, and PHD1 was necessary for P1465 hydroxylation while PHD2 had an inhibitory effect. P1465 hydroxylation was required for oxidative-stress-induced Ser5 phosphorylation of Rpb1. Importantly, overexpression of wild-type Rpb1 stimulated formation of kidney tumors by VHL(+) cells, and this effect was abolished by P1465A mutation of Rpb1. These data indicate that through this novel pathway involving P1465 hydroxylation and Ser5 phosphorylation of Rbp1, pVHL may regulate tumor growth.
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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.