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

Scheffner, Martin, Huibregtse, Jon M., Vierstra, Richard D., Howley, Peter M.·1993·Cell
DOI 10.1016/0092-8674(93)90384-3
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Abstract

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.

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Citations

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Metadata

Authors
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., & Howley, P. M.
Venue
Cell
Publisher
Elsevier BV
Published
1993-11
Volume
75
Issue
3
Pages
495-505
ISSN
0092-8674
DOI
10.1016/0092-8674(93)90384-3
Cited by
2,054
References
4
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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