ArticleProceedings of the National Academy of Sciences of the United States of America2005
Down-regulation of the retinoblastoma tumor suppressor by the hepatitis C virus NS5B RNA-dependent RNA polymerase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Hepatitis C virus infection is associated with high risk of breast cancer: a pooled analysis of 68,014 participants.Frontiers in oncology · 2023Pooled it
- Hijacking the cytoskeleton: association of HCV polymerase with α/β-tubulin and its potential relation to the viral replication and cell proliferation.Molecular and cellular biochemistry · 2026Article
- Modeling in vitro cell-to-cell spread of hepatitis C viral infection using an agent-based approach.bioRxiv : the preprint server for biology · 2026Article
- Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients.Virus research · 2025Article
- Review
- HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article.International journal of molecular sciences · 2023Review
- Regulatory Role of Ribonucleotide Reductase Subunit M2 in Hepatocyte Growth and Pathogenesis of Hepatitis C Virus.International journal of molecular sciences · 2023Review
- Review
- The Four Homeostasis Knights: In Balance upon Post-Translational Modifications.International journal of molecular sciences · 2022Review
- Integrated analysis to study the interplay between post-translational modifications (PTM) in hepatitis C virus proteins and hepatocellular carcinoma (HCC) development.Scientific reports · 2022Article
- Post-translational modifications on the retinoblastoma protein.Journal of biomedical science · 2022Review
- HCV and tumor-initiating stem-like cells.Frontiers in physiology · 2022Review
- Review
- Akt Phosphorylation of Hepatitis C Virus NS5B Regulates Polymerase Activity and Hepatitis C Virus Infection.Frontiers in microbiology · 2021Article
- Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma.World journal of gastroenterology · 2020Review
- Cancer Patients Have a Higher Risk Regarding COVID-19 - and Vice Versa?Pharmaceuticals (Basel, Switzerland) · 2020Article
- Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis.Seminars in cell & developmental biology · 2020Review
- Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment.Journal of hepatocellular carcinoma · 2020Review
- Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.Frontiers in cell and developmental biology · 2020Review
- Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The retinoblastoma tumor-suppressor protein (Rb) plays a critical role in controlling cellular proliferation and apoptosis by regulating E2F transcription factors. Rb is a key target of oncoproteins expressed by DNA tumor viruses, but RNA viruses are not known to regulate Rb function. Here, we show that Rb abundance is negatively regulated in cells containing replicating genomic RNA from hepatitis C virus, a human virus strongly associated with hepatocellular carcinoma. The viral RNA-dependent RNA polymerase NS5B forms a complex with Rb, targeting it for degradation and resulting in reduction of Rb abundance, activation of E2F-responsive promoters, and cell proliferation. NS5B contains a conserved Leu-x-Cys/Asn-x-Asp motif that is homologous to Rb-binding domains in the oncoproteins of DNA viruses. This domain overlaps the polymerase active site, and mutations within it abrogate Rb binding and reverse the effects of NS5B on E2F promoter activation and cell proliferation. These findings suggest a unique link between an oncogenic RNA virus implicated in the development of liver cancer and a critically important tumor-suppressor protein.
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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.