ArticleNature2016
Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 292 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
292 citing papers in PubMed, 2 syntheses or guidelines pooled it, 474 citations in OpenAlex.
- Loss of p53-DREAM-mediated repression of cell cycle genes as a driver of lymph node metastasis in head and neck cancer.Genome medicine · 2023Pooled it
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- From HPV infection to cervical precancer: Molecular mechanisms, immune microenvironment and emerging technologies.Cellular and molecular life sciences : CMLS · 2026Review
- Members of the RhoA subfamily of GTPases suppress the stimulatory effect of the HPV E6 oncoprotein on the ubiquitin ligase E6AP.Scientific reports · 2026Article
- Rethinking residual p53 function in HPV-positive cervical cancer cells.Journal of virology · 2026Article
- Plant Bioactive Constituents and Their Potential Benefits in HPV-Positive Oropharyngeal Squamous Cell Carcinoma-A Narrative Review.Current issues in molecular biology · 2026Review
- 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
- Article
- HPV16 genetic variation provides evidence of positive natural selection driven by HLA class I.Nature communications · 2026Article
- Hepatitis B virus X protein induces E6-associated protein-mediated proteasomal degradation of p53 phosphorylated at Ser-15.The Journal of general virology · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Template-driven scaffolding of SCFNature · 2026Article
- Molecular Dynamics and Docking Reveal Enhanced Binding of HPV16 E6 Asian American Variants To non-phosphorylated DLG1.Cell biochemistry and biophysics · 2026Article
- HPV18E6 and CDK5 virus-host interaction is a prospective therapeutic target for HPV-positive cervical cancer.Tumour virus research · 2026Article
- Characterization of patient-derived HPV16 E6 and E7 variant alleles.Journal of virology · 2026Article
- Integrated computational screening of FDA-approved anticancer drugs as novel HPV-16 E6 inhibitors in cervical cancer.Scientific reports · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- HPV16 E6 oncoprotein promotes microhomology-mediated viral integration by increasing PolΘ protein expression.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synergism on Cancer Development of Human Papillomavirus and Chlamydia Trachomatis Co-Infection.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Article
232 more citing papers are in PubMed but not listed here.
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 6 institutions in 2 countries.
Funding
Abstract
The p53 pro-apoptotic tumour suppressor is mutated or functionally altered in most cancers. In epithelial tumours induced by 'high-risk' mucosal human papilloma viruses, including human cervical carcinoma and a growing number of head-and-neck cancers, p53 is degraded by the viral oncoprotein E6 (ref. 2). In this process, E6 binds to a short leucine (L)-rich LxxLL consensus sequence within the cellular ubiquitin ligase E6AP. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 (ref. 4). Neither E6 nor E6AP are separately able to recruit p53 (refs 3, 5), and the precise mode of assembly of E6, E6AP and p53 is unknown. Here we solve the crystal structure of a ternary complex comprising full-length human papilloma virus type 16 (HPV-16) E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumour suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against oncogenesis mediated by human papilloma virus.
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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.