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PMID: 8090726 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 19 ·1994-09-13 ·Pages 8797-801

Scheffner M, Huibregtse JM, Howley PM

Abstract

The E6 protein of the oncogenic human papillomavirus types 16 and 18 facilitates the rapid degradation of the tumor-suppressor protein p53 via the ubiquitin-dependent proteolytic pathway. The E6 protein binds to a cellular protein of 100 kDa termed E6-AP. The complex of E6 and E6-AP specifically interacts with p53 and induces the ubiquitination of p53 in a reaction which requires the ubiquitin-activating enzyme (E1) and a cellular fraction thought to contain a mammalian ubiquitin-conjugating enzyme (E2). This mammalian E2 activity could be replaced with bacterially expressed UBC8 from Arabidopsis thaliana, which belongs to a subfamily of E2s including yeast UBC4 and UBC5 which are highly conserved at the amino acid level. In this paper we describe the cloning of a human cDNA encoding a human E2 that we have designated UbcH5 and that is related to Arabidopsis UBC8 and the other members of this subfamily. We demonstrate that UbcH5 can function in the E6/E6-AP-induced ubiquitination of p53.

Related Genes
HHR6A UBC1 UBC4 UBC8 UbcD1 UbcH5 ubc-2
MeSH Terms
Amino Acid Sequence Base Sequence Cloning, Molecular DNA, Complementary/genetics Ligases/genetics,metabolism Molecular Sequence Data Sequence Alignment Sequence Homology, Amino Acid Tumor Suppressor Protein p53/metabolism Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases Ubiquitins/metabolism Viral Proteins/metabolism
Chemicals
DNA, Complementary Tumor Suppressor Protein p53 Ubiquitins Viral Proteins Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Scheffner M
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Huibregtse J M
Howley P M
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37 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.19.8797
Published
1994-09-13
Pages
8797-801
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44693
Subset
IM
Databases
GENBANK
X78140
External Links
PubMed source DOI: 10.1073/pnas.91.19.8797 PMC Full Text View journal details
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