ArticleProceedings of the National Academy of Sciences of the United States of America2019
Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Pooled it
- Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial.Journal of the National Cancer Institute · 2021Trial
- Riddle syndrome with RNF168 mutation in first Asian family cluster exhibiting pulmonary fibrosis and achalasia.Journal of human genetics · 2026Article
- The polymerase milieu of human papillomavirus.Journal of virology · 2026Review
- Viruses and the host replisome: discovering oncogenic mechanisms of small DNA tumor viruses.Journal of virology · 2026Review
- Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication.Virologica Sinica · 2025Article
- Ubiquitination of the histone variant mH2A1.2 prevents toxic RAD18 accumulation at a subset of genomic loci upon replication stress.Molecular cell · 2025Article
- Treatment strategies in human papillomavirus-related advanced penile cancer.Nature reviews. Urology · 2025Review
- Tumor-intrinsic and immune-related features associated with treatment failure in human papillomavirus-related oropharyngeal cancer.Journal of the National Cancer Institute · 2025Article
- Advances in understanding the mechanisms of the human papillomavirus oncoproteins.Biochemical Society transactions · 2025Review
- Human papilloma virus (HPV) mediated cancers: an insightful update.Journal of translational medicine · 2025Review
- How human papillomavirus (HPV) targets DNA repair pathways for viral replication: from guardian to accomplice.Microbiology and molecular biology reviews : MMBR · 2025Review
- Review
- Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use.Signal transduction and targeted therapy · 2025Review
- The roles of DNA damage repair and innate immune surveillance pathways in HPV pathogenesis.Virology · 2024Review
- Association of oropharyngeal cancer recurrence with tumor-intrinsic and immune-mediated sequelae of reduced genomic instability.bioRxiv : the preprint server for biology · 2024Article
- Functional RNAi Screening Identifies G2/M and Kinetochore Components as Modulators of TNFα/NF-κB Prosurvival Signaling in Head and Neck Squamous Cell Carcinoma.Cancer research communications · 2024Article
- HPV and HCMV in Cervical Cancer: A Review of Their Co-Occurrence in Premalignant and Malignant Lesions.Viruses · 2024Review
- HPV16 E6-induced M2 macrophage polarization in the cervical microenvironment via exosomal miR-204-5p.Scientific reports · 2024Article
- E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer.Oncogene · 2024Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
High-risk human papillomaviruses (HR-HPVs) promote cervical cancer as well as a subset of anogenital and head and neck cancers. Due to their limited coding capacity, HPVs hijack the host cell's DNA replication and repair machineries to replicate their own genomes. How this host-pathogen interaction contributes to genomic instability is unknown. Here, we report that HPV-infected cancer cells express high levels of RNF168, an E3 ubiquitin ligase that is critical for proper DNA repair following DNA double-strand breaks, and accumulate high numbers of 53BP1 nuclear bodies, a marker of genomic instability induced by replication stress. We describe a mechanism by which HPV E7 subverts the function of RNF168 at DNA double-strand breaks, providing a rationale for increased homology-directed recombination in E6/E7-expressing cervical cancer cells. By targeting a new regulatory domain of RNF168, E7 binds directly to the E3 ligase without affecting its enzymatic activity. As RNF168 knockdown impairs viral genome amplification in differentiated keratinocytes, we propose that E7 hijacks the E3 ligase to promote the viral replicative cycle. This study reveals a mechanism by which tumor viruses reshape the cellular response to DNA damage by manipulating RNF168-dependent ubiquitin signaling. Importantly, our findings reveal a pathway by which HPV may promote the genomic instability that drives oncogenesis.
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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.