ArticleProceedings of the National Academy of Sciences of the United States of America2003
von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 232 citations in OpenAlex.
- 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
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- Microtubule dynamics is a therapeutic vulnerability in VHL-deficient renal cell carcinoma.International journal of biological sciences · 2025Article
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.Scientific reports · 2024Article
- Differential processing of RNA polymerase II at DNA damage correlates with transcription-coupled repair syndrome severity.Nucleic acids research · 2024Article
- DNA break induces rapid transcription repression mediated by proteasome-dependent RNAPII removal.Cell reports · 2024Article
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.bioRxiv : the preprint server for biology · 2024Article
- ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans.Genome biology · 2024Article
- The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Development of VHL-recruiting STING PROTACs that suppress innate immunity.Cellular and molecular life sciences : CMLS · 2023Article
- VHL tumor suppressor as a novel potential candidate biomarker in papillary thyroid carcinoma.Biomolecules & biomedicine · 2023Review
- Regulation of RNA Polymerase I Stability and Function.Cancers · 2022Review
- 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
- DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II.Nature communications · 2022Article
- ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia.Nucleic acids research · 2022Article
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31 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The transition from transcription initiation to elongation involves phosphorylation of the large subunit (Rpb1) of RNA polymerase II on the repetitive carboxyl-terminal domain. The elongating hyperphosphorylated Rpb1 is subject to ubiquitination, particularly in response to UV radiation and DNA-damaging agents. By using computer modeling, we identified regions of Rpb1 and the adjacent subunit 6 of RNA polymerase II (Rpb6) that share sequence and structural similarity with the domain of hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) that binds von Hippel-Lindau tumor suppressor protein (pVHL). pVHL confers substrate specificity to the E3 ligase complex, which ubiquitinates HIF-alpha and targets it for proteasomal degradation. In agreement with the computational model, we show biochemical evidence that pVHL specifically binds the hyperphosphorylated Rpb1 in a proline-hydroxylation-dependent manner, targeting it for ubiquitination. This interaction is regulated by UV radiation.
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Registered trials
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.