ArticlePLoS pathogens2017
Cutaneous HPV8 and MmuPV1 E6 Proteins Target the NOTCH and TGF-β Tumor Suppressors to Inhibit Differentiation and Sustain Keratinocyte Proliferation.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review.Current medicinal chemistry · 2025Pooled it
- MmuPV1 E7 promotes phenotypes associated with "high-risk" HPV infection in mouse keratinocytes.Journal of virology · 2025Article
- E2 Tyrosine 102 Regulates MmuPV1 Pathogenesis In Vivo.Pathogens (Basel, Switzerland) · 2025Article
- Opinion: Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin.Frontiers in microbiology · 2025Article
- Article
- mSphere of Influence: MmuPV1-a dual tropic papillomavirus, red herring, or novel insight into HPV pathogenesis.mSphere · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model.Pathogens (Basel, Switzerland) · 2023Article
- Review
- Human papillomaviruses: Knowns, mysteries, and unchartered territories.Journal of medical virology · 2023Review
- The antiviral effects of a MEK1/2 inhibitor promote tumor regression in a preclinical model of human papillomavirus infection-induced tumorigenesis.Antiviral research · 2023Article
- HPV E6 inhibits E6AP to regulate epithelial homeostasis by modulating keratinocyte differentiation commitment and YAP1 activation.PLoS pathogens · 2023Article
- Androgen promotes squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3-dependent pathway.Cancer medicine · 2023Article
- MmuPV1 E7's interaction with PTPN14 delays Epithelial differentiation and contributes to virus-induced skin disease.PLoS pathogens · 2023Article
- Stress keratin 17 and estrogen support viral persistence and modulate the immune environment during cervicovaginal murine papillomavirus infection.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Beta Human Papillomavirus 8 E6 Induces Micronucleus Formation and Promotes Chromothripsis.Journal of virology · 2022Article
- FOXP4 inhibits squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3-dependent pathway.Cancer science · 2022Article
- Review
- MmuPV1-Induced Cutaneous Squamous Cell Carcinoma Arises Preferentially from Lgr5+ Epithelial Progenitor Cells.Viruses · 2022Article
- Expanded Basal Compartment and Disrupted Barrier in Vocal Fold Epithelium Infected with Mouse Papillomavirus MmuPV1.Viruses · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cutaneous beta-papillomaviruses are associated with non-melanoma skin cancers that arise in patients who suffer from a rare genetic disorder, Epidermodysplasia verruciformis (EV) or after immunosuppression following organ transplantation. Recent studies have shown that the E6 proteins of the cancer associated beta human papillomavirus (HPV) 5 and HPV8 inhibit NOTCH and TGF-β signaling. However, it is unclear whether disruption of these pathways may contribute to cutaneous HPV pathogenesis and carcinogenesis. A recently identified papillomavirus, MmuPV1, infects laboratory mouse strains and causes cutaneous skin warts that can progress to squamous cell carcinoma. To determine whether MmuPV1 may be an appropriate model to mechanistically dissect the molecular contributions of cutaneous HPV infections to skin carcinogenesis, we investigated whether MmuPV1 E6 shares biological and biochemical activities with HPV8 E6. We report that the HPV8 and MmuPV1 E6 proteins share the ability to bind to the MAML1 and SMAD2/SMAD3 transcriptional cofactors of NOTCH and TGF-beta signaling, respectively. Moreover, we demonstrate that these cutaneous papillomavirus E6 proteins inhibit these two tumor suppressor pathways and that this ability is linked to delayed differentiation and sustained proliferation of differentiating keratinocytes. Furthermore, we demonstrate that the ability of MmuPV1 E6 to bind MAML1 is necessary for papilloma formation in experimentally infected mice. Our results, therefore, suggest that experimental MmuPV1 infection in mice will be a robust and useful experimental system to model key aspects of cutaneous HPV infection, pathogenesis and carcinogenesis.
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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.