Reconstitution of p53-ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP).
The E6 protein of the high-risk human papillomaviruses inactivates the tumor suppressor protein p53 by stimulating its ubiquitinylation and subsequent degradation. Ubiquitinylation is a multistep process involving a ubiquitin-activating enzyme, one of many distinct ubiquitin-conjugating enzymes, and in certain cases, a ubiquitin ligase. In human papillomavirus-infected cells, E6 and the ... E6-associated protein are thought to act as a ubiquitin-protein ligase in the ubiquitinylation of p53. Here we describe the cloning of a human ubiquitin-conjugating enzyme that specifically ubiquitinylates E6-associated protein. Furthermore, we define the biochemical pathway of p53 ubiquitinylation and demonstrate that in vivo inhibition of various components in the pathway leads to an inhibition of E6-stimulated p53 degradation.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Cloning, Molecular, Fluorescent Antibody Technique, HeLa Cells, Humans, Ligases, Microinjections, Molecular Sequence Data, Recombinant Proteins, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Tumor Suppressor Protein p53, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitins, Viral Proteins
Amino Acid Sequence, Base Sequence, Cloning, Molecular, Fluorescent Antibody Technique, HeLa Cells, Humans, Ligases, Microinjections, Molecular Sequence Data, Recombinant Proteins, Sequence Analysis, DNA, 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: Apr. 11, 1995
PubMed ID: 7724550
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