ArticlePLoS pathogens2019
E6 proteins from high-risk HPV, low-risk HPV, and animal papillomaviruses activate the Wnt/β-catenin pathway through E6AP-dependent degradation of NHERF1.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
38 citing papers in PubMed, 59 citations in OpenAlex.
- Hippo pathway disruption and YAP1 activation in anogenital papillary squamous intraepithelial lesion.Histopathology · 2026Article
- Members of the RhoA subfamily of GTPases suppress the stimulatory effect of the HPV E6 oncoprotein on the ubiquitin ligase E6AP.Scientific reports · 2026Article
- Covalent inhibitors of human papillomavirus type 16 E6 protein restore p53 function and suppress growth of HPV-driven tumors in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Review
- Review
- E6AP is essential for the proliferation of HPV-positive cancer cells by preventing senescence.PLoS pathogens · 2025Article
- Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use.Signal transduction and targeted therapy · 2025Review
- PATHOMORPHOLOGY OF VERRUCAE: A CLINICOPATHOLOGIC STUDY.Annals of Ibadan postgraduate medicine · 2024Article
- LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma.BMC women's health · 2024Article
- The potential role of HPV oncoproteins in the PD-L1/PD-1 pathway in cervical cancer: new perspectives on cervical cancer immunotherapy.Frontiers in oncology · 2024Review
- Genome composition-based deep learning predicts oncogenic potential of HPVs.Frontiers in cellular and infection microbiology · 2024Article
- Molecular aspects of cervical cancer: a pathogenesis update.Frontiers in oncology · 2024Review
- Review
- Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions.MedComm · 2023Review
- HPV16 Impacts NHERF2 Expression in Oropharyngeal Cancers.Pathogens (Basel, Switzerland) · 2023Article
- HPV E6 inhibits E6AP to regulate epithelial homeostasis by modulating keratinocyte differentiation commitment and YAP1 activation.PLoS pathogens · 2023Article
- Review
- Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.Protein science : a publication of the Protein Society · 2023Article
- Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
High-risk human papillomavirus (HPV) E6 proteins associate with the cellular ubiquitin ligase E6-Associated Protein (E6AP), and then recruit both p53 and certain cellular PDZ proteins for ubiquitination and degradation by the proteasome. Low-risk HPV E6 proteins also associate with E6AP, yet fail to recruit p53 or PDZ proteins; their E6AP-dependent targets have so far been uncharacterized. We found a cellular PDZ protein called Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) is targeted for degradation by both high and low-risk HPV E6 proteins as well as E6 proteins from diverse non-primate mammalian species. NHERF1 was degraded by E6 in a manner dependent upon E6AP ubiquitin ligase activity but independent of PDZ interactions. A novel structural domain of E6, independent of the p53 recognition domain, was necessary to associate with and degrade NHERF1, and the NHERF1 EB domain was required for E6-mediated degradation. Degradation of NHERF1 by E6 activated canonical Wnt/β-catenin signaling, a key pathway that regulates cell growth and proliferation. Expression levels of NHERF1 increased with increasing cell confluency. This is the first study in which a cellular protein has been identified that is targeted for degradation by both high and low-risk HPV E6 as well as E6 proteins from diverse animal papillomaviruses. This suggests that NHERF1 plays a role in regulating squamous epithelial growth and further suggests that the interaction of E6 proteins with NHERF1 could be a common therapeutic target for multiple papillomavirus types.
Indexed as
Identifiers
What OpenQuestion holds
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.