The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53.
The ubiquitin-dependent proteolytic pathway plays a major role in selective protein degradation. Ubiquitination of proteins requires the sequential action of the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (E2), and in some cases ubiquitin-protein ligases (E3s). The oncogenic human papillomavirus (HPV) types 16 and 18 utilize this cellular proteolytic system to target ... the tumor suppressor protein p53. The HPV E6 oncoprotein binds to a cellular protein of 100 kd, termed E6-associated protein (E6-AP). The E6-E6-AP complex specifically interacts with p53, resulting in the rapid ubiquitin-dependent degradation of p53. Here we report the purification and identification of the factors necessary for the E6-E6-AP-mediated ubiquitination of p53. The ubiquitination of p53 requires the E1 enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex. Furthermore, E6-AP appears to have ubiquitin-protein ligase activity in the absence of E6.
Mesh Terms:
Cell Line, Humans, Ligases, Macromolecular Substances, Models, Biological, Oncogene Proteins, Viral, Recombinant Fusion Proteins, Repressor Proteins, Tumor Suppressor Protein p53, Ubiquinone, Ubiquitin-Activating Enzymes, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Viral Proteins
Cell Line, Humans, Ligases, Macromolecular Substances, Models, Biological, Oncogene Proteins, Viral, Recombinant Fusion Proteins, Repressor Proteins, Tumor Suppressor Protein p53, Ubiquinone, Ubiquitin-Activating Enzymes, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Viral Proteins
Cell
Date: Nov. 05, 1993
PubMed ID: 8221889
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