Cited by 879Cancer-related Molecular PathwaysCervical Cancer and HPV ResearchUbiquitin and proteasome pathways

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A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18.

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Huibregtse, J.M., Scheffner, M., Howley, P.M.·1991·The EMBO Journal

DOI 10.1002/j.1460-2075.1991.tb04990.xPMC PMC453163

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Abstract

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)
ORCID: Huibregtse, J.M.
Scheffner, M.
Howley, P.M.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1991-12-01
Volume: 10
Issue: 13
Pages: 4129-4135
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1002/j.1460-2075.1991.tb04990.x
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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

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A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18.

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