A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18.
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The E6 protein of human papillomavirus types 16 and 18 (HPV-16 and HPV-18) can stably associate with the p53 protein in vitro. In the presence of rabbit reticulocyte lysate, this association leads to the specific degradation of p53 through the ubiquitin-dependent proteolysis system. We have examined the E6-p53 complex in more detail and have found that association of E6 with p53 is mediated by an additional cellular factor. This factor is present in rabbit reticulocyte lysate, primary human keratinocytes and in each of five human cell lines examined. The factor is designated E6-AP, for E6-associated protein, based on the observation that the E6 proteins of HPV-16 and 18 can form a stable complex with the factor in the absence of p53, whereas p53 association with the factor can be detected only in the presence of E6. Gel filtration and coprecipitation experiments indicate that E6-AP is a monomeric protein of approximately 100 kDa.
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- Authors
- Huibregtse, J. M., Scheffner, M., & Howley, P. M.
- Affiliations
- National Institutes of Health (US)
- Venue
- The EMBO Journal
- Published
- 1991-12-01
- Volume
- 10
- Issue
- 13
- Pages
- 4129-4135
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC453163
- OpenAlex
- W140061535
- Cited by
- 879
- References
- 46
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 16 · 2023: 26 · 2022: 21 · 2021: 25 · 2020: 27 · 2019: 18 · 2018: 28 · 2017: 29 · 2016: 19 · 2015: 26 · 2014: 29 · 2013: 28 · 2012: 41
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- p53, E6 oncoprotein, HPV16, HPV 18, UBE3A, ubiquitin-mediated proteolysis, p53 degradation, protein-protein interaction, keratinocytes, tumor suppressor
- MeSH terms
- Animals, Cell Line, Chromatography, Gel, DNA-Binding Proteins, Electrophoresis, Polyacrylamide Gel, Humans, Hydrolysis, Oncogene Proteins, Viral, Plasmids, Protein Binding, Proteins, Repressor Proteins, Reticulocytes, Tumor Suppressor Protein p53, Papillomaviridae
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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