The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53

M Scheffner, JM Huibregtse, RD Vierstra, PM Howley - Cell, 1993 - cell.com
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 (El), ubiquitin-conjugating enzymes (E2), and in some cases ubiquitin-
protein ligases (E3s). The oncogenic human papillomavirus (HPV) types 16 and 16 utilize
this cellular proteolytic system to target the tumor suppressor protein~ 53. The HPV E6
oncoprotein binds to a cellular protein of 100 kd, termed EG-associated protein (EG-AP) …
Summary
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 (El), ubiquitin-conjugating enzymes (E2), and in some cases ubiquitin-protein ligases (E3s). The oncogenic human papillomavirus (HPV) types 16 and 16 utilize this cellular proteolytic system to target the tumor suppressor protein~ 53. The HPV E6 oncoprotein binds to a cellular protein of 100 kd, termed EG-associated protein (EG-AP). The E6-EG-AP complex specifically interacts with~ 53, resulting in the rapid ubiquitin-dependent degradation of~ 53. Here we report the purification and identification of the factors necessary for the E6-E6-AP-mediated ubiquitination of~ 53. The ubiquitination of~ 53 requires the El enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex. Furthermore, EG-AP appears to have ubiquitin-protein ligase activity in the absence of E6.
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