TY - JOUR
T1 - Reconstitution of p53-ubiquitinylation reactions from purified components
T2 - The role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP)
AU - Rolfe, Mark
AU - Beer-Romero, Peggy
AU - Glass, Susan
AU - Eckstein, Jens
AU - Berdo, Ingrid
AU - Theodoras, Annie
AU - Pagano, Michele
AU - Draetta, Giulio
PY - 1995/4/11
Y1 - 1995/4/11
N2 - 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.
AB - 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.
KW - cervical cancer
KW - degradation
KW - human papilloma virus
UR - http://www.scopus.com/inward/record.url?scp=0028939392&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028939392&partnerID=8YFLogxK
U2 - 10.1073/pnas.92.8.3264
DO - 10.1073/pnas.92.8.3264
M3 - Article
C2 - 7724550
AN - SCOPUS:0028939392
SN - 0027-8424
VL - 92
SP - 3264
EP - 3268
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -