Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53.
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.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Cloning, Molecular, DNA, Complementary, Ligases, Molecular Sequence Data, Sequence Alignment, Sequence Homology, Amino Acid, Tumor Suppressor Protein p53, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitins, Viral Proteins
Amino Acid Sequence, Base Sequence, Cloning, Molecular, DNA, Complementary, Ligases, Molecular Sequence Data, Sequence Alignment, Sequence Homology, Amino Acid, Tumor Suppressor Protein p53, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitins, Viral Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Sep. 13, 1994
PubMed ID: 8090726
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