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PMID: 1321031 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.

The EMBO journal ·Vol. 11 ·No. 7 ·1992-07-00 ·Pages 2425-31

Scheffner M, Münger K, Huibregtse JM, Howley PM

Abstract

The E6 and the E7 proteins of the oncogenic human papillomavirus types 16 and 18 can stably associate with p53 and the retinoblastoma protein, respectively. The E6-p53 interaction results in the accelerated degradation of p53 in vitro via the ubiquitin-dependent proteolysis system. In this study we demonstrate that a fusion protein consisting of the N-terminal half of the HPV-16 E7 protein and the full length HPV-16 E6 protein promotes the in vitro degradation of the retinoblastoma protein. This indicates that the property of the HPV-16 E6 protein to stimulate the degradation of p53 can be targeted to other proteins. Unlike the HPV-16 or HPV-18 E6 protein, the E6 proteins of HPV-6 and 11 do not bind to p53 and consequently do not target p53 for degradation. Analogous E7-E6 fusion proteins using the E6 proteins of HPV-6 and HPV-11, however, also have the ability to promote the degradation of the retinoblastoma protein, indicating that the property to target associated proteins for degradation is shared by the anogenital specific HPV E6 proteins.

MeSH Terms
Base Sequence DNA DNA-Binding Proteins Electrophoresis, Polyacrylamide Gel Humans Hydrolysis Molecular Sequence Data Oncogene Proteins, Viral/metabolism Papillomaviridae/metabolism Papillomavirus E7 Proteins Plasmids Precipitin Tests Recombinant Fusion Proteins/metabolism Repressor Proteins Retinoblastoma Protein/metabolism Tumor Suppressor Protein p53/metabolism
Chemicals
DNA-Binding Proteins E6 protein, Human papillomavirus type 16 E7 protein, Human papillomavirus type 18 Oncogene Proteins, Viral Papillomavirus E7 Proteins Recombinant Fusion Proteins Repressor Proteins Retinoblastoma Protein Tumor Suppressor Protein p53 oncogene protein E7, Human papillomavirus type 16 DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Scheffner M
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892.
Münger K
Huibregtse J M
Howley P M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-07-00
Pages
2425-31
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556717
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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