TY - JOUR
T1 - Human papillomavirus E7 oncoproteins bind a single form of cyclin E in a complex with cdk2 and p107
AU - McIntyre, Maritza C.
AU - Ruesch, Margaret N.
AU - Laimins, Laimonis A.
N1 - Funding Information:
We thank Nicholas Dyson, Mark Ewen, Nissim Hay, Tony Hunter, Emma Lees, and James Roberts for sharing valuable reagents. We also are grateful to Jonathan Green and Larry Boise for their assistance in FACS analysis and to the members of the Laimins laboratory for helpful discussions. In addition, we thank Kathy Rundell, Richard Longnecker, Dennis McCance, and Mark Frattini for helpful advice on the manuscript. This work was supported by grants from the National Cancer Institute (CA60607) and the National Institutes of Allergy and Infectious Deseases (UO1 AI31494) to L.A.L.
PY - 1996/1/1
Y1 - 1996/1/1
N2 - The E6 and E7 proteins of the high-risk human papillomaviruses (HPVs) act coordinately to immortalize human keratinocytes. These viral oncoproteins function by binding and altering the activity of cellular proteins which regulate cell cycle progression. Among the proteins bound by E7 are the retinoblastoma protein, Rb, as well as the related p107 and p130 proteins. In addition, E7 binds cyclin A, which regulates transit through the S and G2/M phases of the cell cycle. In this study, we demonstrate that HPV 18 E7 also associates with cyclin E which controls the G1/S transition. E7/cyclin E complexes were immunoprecipitated from E7-expressing cells as well as from cell extracts using GST-E7 fusion proteins. E7 was found to complex with a single form of cyclin E, and the binding was mediated through p107. Both E7/cyclin E and E7/cyclin A complexes exhibit kinase activity through associated cdk2 proteins which can contribute to phosphorylation of p107. The association of E7 with proteins which regulate transit through the cell cycle may provide an additional mechanism by which infection with human papillomaviruses results in cellular hyperproliferation.
AB - The E6 and E7 proteins of the high-risk human papillomaviruses (HPVs) act coordinately to immortalize human keratinocytes. These viral oncoproteins function by binding and altering the activity of cellular proteins which regulate cell cycle progression. Among the proteins bound by E7 are the retinoblastoma protein, Rb, as well as the related p107 and p130 proteins. In addition, E7 binds cyclin A, which regulates transit through the S and G2/M phases of the cell cycle. In this study, we demonstrate that HPV 18 E7 also associates with cyclin E which controls the G1/S transition. E7/cyclin E complexes were immunoprecipitated from E7-expressing cells as well as from cell extracts using GST-E7 fusion proteins. E7 was found to complex with a single form of cyclin E, and the binding was mediated through p107. Both E7/cyclin E and E7/cyclin A complexes exhibit kinase activity through associated cdk2 proteins which can contribute to phosphorylation of p107. The association of E7 with proteins which regulate transit through the cell cycle may provide an additional mechanism by which infection with human papillomaviruses results in cellular hyperproliferation.
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U2 - 10.1006/viro.1996.0008
DO - 10.1006/viro.1996.0008
M3 - Article
C2 - 8553588
AN - SCOPUS:0030058803
SN - 0042-6822
VL - 215
SP - 73
EP - 82
JO - Virology
JF - Virology
IS - 1
ER -