Cited by 3,995Cancer-related Molecular PathwaysCervical Cancer and HPV ResearchUbiquitin and proteasome pathways

The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53

Scheffner, Martin, Werness, Bruce A., Huibregtse, Jon M., Levine, Arnold J., Howley, Peter M.·1990·Cell

Abstract

The E6 protein encoded by the oncogenic human papillomavirus types 16 and 18 is one of two viral products expressed in HPV-associated cancers. E6 is an oncoprotein which cooperates with E7 to immortalize primary human keratinocytes. Insight into the mechanism by which E6 functions in oncogenesis is provided by the observation that the E6 protein encoded by HPV-16 and HPV-18 can complex the wild-type p53 protein in vitro. Wild-type p53 gene has tumor suppressor properties, and is a target for several of the oncoproteins encoded by DNA tumor viruses. In this study we demonstrate that the E6 proteins of the oncogenic HPVs that bind p53 stimulate the degradation of p53. The E6-promoted degradation of p53 is ATP dependent and involves the ubiquitin-dependent protease system. Selective degradation of cellular proteins such as p53 with negative regulatory functions provides a novel mechanism of action for dominant-acting oncoproteins.

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Crossref · 10.1016/0092-8674(90)90409-8

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  • Human papillomavirus protein E6 induces interactions between TP53 and E6-associated protein (E6-AP).

    “Studying the human papillomavirus protein E6, they discovered that E6 induces interactions between two host proteins: TP53, involved in viral surveillance, and one that they named E6-associated protein (E6-AP).”

    From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [93]

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Authors
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J., & Howley, P. M.
Affiliations
  • National Cancer Institute (US)
  • Princeton University (US)
Venue
Cell
Publisher
Elsevier BV
Published
1990-12
Volume
63
Issue
6
Pages
1129-1136
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2039382131
Cited by
3,995
References
54
Citations by year
2026: 68 · 2025: 62 · 2024: 68 · 2023: 87 · 2022: 85 · 2021: 87 · 2020: 98 · 2019: 91 · 2018: 97 · 2017: 103 · 2016: 102 · 2015: 105 · 2014: 107 · 2013: 112 · 2012: 156
FWCI
39.96
Type
journal article
Language
en
Open access
closed
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
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
E6 oncoprotein, HPV16, HPV 18, p53 degradation, ubiquitin-mediated proteolysis, tumor suppressor proteins, HPV-associated cancers, keratinocyte immortalization
MeSH terms
Antigens, Polyomavirus Transforming, DNA-Binding Proteins, Humans, Oncogene Proteins, Viral, Endopeptidases, Protein Binding, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, Ubiquitins, Blotting, Western, Tumor Suppressor Protein p53, Papillomaviridae

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