ArticleMicrobiology spectrum2022
A Critical Role for p53 during the HPV16 Life Cycle.
Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- In silico analysis of driver genes in squamous cell carcinoma of the cervix: insights into their biological functions, prognosis, immune infiltration, and therapy.World journal of surgical oncology · 2026Article
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- The utility of fibroblast co-culture for the maintenance of episomes in human papillomavirus-associated cancer models.mSphere · 2026Article
- Article
- The Utility of Fibroblast Co-culture for the Maintenance of Episomes in Human Papillomavirus-Associated Cancer Models.bioRxiv : the preprint server for biology · 2025Article
- Article
- Human cytomegalovirus infection coopts chromatin organization to diminish TEAD1 transcription factor activity.bioRxiv : the preprint server for biology · 2025Article
- How human papillomavirus (HPV) targets DNA repair pathways for viral replication: from guardian to accomplice.Microbiology and molecular biology reviews : MMBR · 2025Review
- ELF3 Overexpression Contributes to the Malignant Transformation of HPV16 E6/E7-Immortalized Keratinocytes by Promoting CCNE2 Expression.Journal of microbiology and biotechnology · 2024Article
- PinX1 plays multifaceted roles in human cancers: a review and perspectives.Molecular biology reports · 2024Review
- Fibroblast stromal support model for predicting human papillomavirus-associated cancer drug responses.Journal of virology · 2024Article
- Fibroblasts Regulate the Transformation Potential of Human Papillomavirus-positive Keratinocytes.bioRxiv : the preprint server for biology · 2024Article
- Senataxin mediates R-loop resolution on HPV episomes.Journal of virology · 2024Article
- Article
- Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.Cells · 2024Review
- Article
- Mechanistic Contributions of lncRNAs to Cellular Signaling Pathways Crucial to the Lifecycle of Human Papillomaviruses.Viruses · 2022Review
- Human papillomavirus 16 E2 blocks cellular senescence in response to activation of the DNA damage response.Virology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Human papillomaviruses (HPV) are causative agents in ano-genital and oral cancers; HPV16 is the most prevalent type detected in human cancers. The HPV16 E6 protein targets p53 for proteasomal degradation to facilitate proliferation of the HPV16 infected cell. However, in HPV16 immortalized cells E6 is predominantly spliced (E6*) and unable to degrade p53. Here, we demonstrate that human foreskin keratinocytes immortalized by HPV16 (HFK+HPV16), and HPV16 positive oropharyngeal cancers, retain significant expression of p53. In addition, p53 levels increase in HPV16+ head and neck cancer cell lines following treatment with cisplatin. Introduction of full-length E6 into HFK+HPV16 resulted in attenuation of cellular growth (in hTERT immortalized HFK, E6 expression promoted enhanced proliferation). An understudied interaction is that between E2 and p53 and we investigated whether this was important for the viral life cycle. We generated mutant genomes with E2 unable to interact with p53 resulting in profound phenotypes in primary HFK. The mutant induced hyper-proliferation, but an ultimate arrest of cell growth; β-galactosidase staining demonstrated increased senescence, and COMET assays showed increased DNA damage compared with HFK+HPV16 wild-type cells. There was failure of the viral life cycle in organotypic rafts with the mutant HFK resulting in premature differentiation and reduced proliferation. The results demonstrate that p53 expression is critical during the HPV16 life cycle, and that this may be due to a functional interaction between E2 and p53. Disruption of this interaction has antiviral potential.
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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.