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PMID: 8380895 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53.

Molecular and cellular biology ·Vol. 13 ·No. 2 ·1993-02-00 ·Pages 775-84

Huibregtse JM, Scheffner M, Howley PM

Abstract

The E6 oncoproteins of the cancer-associated or high-risk human papillomaviruses (HPVs) target the cellular p53 protein. The association of E6 with p53 leads to the specific ubiquitination and degradation of p53 in vitro, suggesting a model by which E6 deregulates cell growth control by the elimination of the p53 tumor suppressor protein. Complex formation between E6 and p53 requires an additional cellular factor, designated E6-AP (E6-associated protein), which has a native and subunit molecular mass of approximately 100 kDa. Here we report the purification of E6-AP and the cloning of its corresponding cDNA, which contains a novel open reading frame encoding 865 amino acids. E6-AP, translated in vitro, has the following properties: (i) it associates with wild-type p53 in the presence of the HPV16 E6 protein and simultaneously stimulates the association of E6 with p53, (ii) it associates with the high-risk HPV16 and HPV18 E6 proteins in the absence of p53, and (iii) it induces the E6- and ubiquitin-dependent degradation of p53 in vitro.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cloning, Molecular DNA, Viral Humans Molecular Sequence Data Oncogene Proteins, Viral/metabolism Papillomaviridae/genetics,metabolism Protein Biosynthesis Rats Repressor Proteins Sequence Homology, Amino Acid Tumor Suppressor Protein p53/metabolism Ubiquitin-Protein Ligases Viral Proteins/genetics,isolation & purification,metabolism
Chemicals
DNA, Viral E6 protein, Human papillomavirus type 16 Oncogene Proteins, Viral Repressor Proteins Tumor Suppressor Protein p53 Viral Proteins UBE3A protein, human Ubiquitin-Protein Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Huibregtse J M
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Scheffner M
Howley P M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.2.775-784.1993
Published
1993-02-00
Pages
775-84
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358960
Subset
IM
Databases
GENBANK
L07557
External Links
PubMed source DOI: 10.1128/mcb.13.2.775-784.1993 PMC Full Text View journal details
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