ArticleAngewandte Chemie (International ed. in English)2015
Targeting the Two Oncogenic Functional Sites of the HPV E6 Oncoprotein with a High-Affinity Bivalent Ligand.
Article in Angewandte Chemie (International ed. in English), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 37 citations in OpenAlex.
- DARPin-induced reactivation of p53 in HPV-positive cells.Nature structural & molecular biology · 2025Article
- Human papilloma virus (HPV) mediated cancers: an insightful update.Journal of translational medicine · 2025Review
- Structure of the p53 degradation complex from HPV16.Nature communications · 2024Article
- Discovery of reactive peptide inhibitors of human papillomavirus oncoprotein E6.Chemical science · 2023Article
- Conformational buffering underlies functional selection in intrinsically disordered protein regions.Nature structural & molecular biology · 2022Article
- Virus against virus: strategies for using adenovirus vectors in the treatment of HPV-induced cervical cancer.Acta pharmacologica Sinica · 2021Review
- Targeting PDZ domains as potential treatment for viral infections, neurodegeneration and cancer.Biology direct · 2021Review
- PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6.Molecules (Basel, Switzerland) · 2021Review
- Hierarchized phosphotarget binding by the seven human 14-3-3 isoforms.Nature communications · 2021Article
- Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers.Frontiers in immunology · 2021Review
- Article
- Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules.Nature communications · 2019Article
- Identification of potential binding pocket on viral oncoprotein HPV16 E6: a promising anti-cancer target for small molecule drug discovery.BMC molecular and cell biology · 2019Article
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Single-Domain Antibodies Represent Novel Alternatives to Monoclonal Antibodies as Targeting Agents against the Human Papillomavirus 16 E6 Protein.International journal of molecular sciences · 2019Article
- Review
- Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97.Viruses · 2018Article
- Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein.Oncotarget · 2017Article
- A novel intracellular antibody against the E6 oncoprotein impairs growth of human papillomavirus 16-positive tumor cells in mouse models.Oncotarget · 2016Article
- Viral Interactions with PDZ Domain-Containing Proteins-An Oncogenic Trait?Pathogens (Basel, Switzerland) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The E6 oncoproteins of high-risk mucosal (hrm) human papillomaviruses (HPVs) contain a pocket that captures LxxLL motifs and a C-terminal motif that recruits PDZ domains, with both functions being crucial for HPV-induced oncogenesis. A chimeric protein was built by fusing a PDZ domain and an LxxLL motif, both known to bind E6. NMR spectroscopy, calorimetry and a mammalian protein complementation assay converged to show that the resulting PDZ-LxxLL chimera is a bivalent nanomolar ligand of E6, while its separated PDZ and LxxLL components are only micromolar binders. The chimera binds to all of the hrm-HPV E6 proteins tested but not to low-risk mucosal or cutaneous HPV E6. Adenovirus-mediated expression of the chimera specifically induces the death of HPV-positive cells, concomitant with increased levels of the tumour suppressor P53, its transcriptional target p21, and the apoptosis marker cleaved caspase 3. The bifunctional PDZ-LxxLL chimera opens new perspectives for the diagnosis and treatment of HPV-induced cancers.
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.