Bovine papillomavirus E7 oncoprotein inhibits anoikis.
The bovine papillomavirus type 1 (BPV-1) E7 oncoprotein is required for the full transformation activity of the virus. Although BPV-1 E7 by itself is not sufficient to induce cellular transformation, it enhances the abilities of the other BPV-1 oncogenes to induce anchorage independence. We have been exploring the mechanisms by which E7 might affect the transformation efficiency of other viral oncoproteins and in particular whether it might protect cells from apoptosis. We report here that BPV-1 E6 and E7 can each independently inhibit anoikis, a type of apoptosis that is induced upon cell detachment. Using site-directed mutagenesis, we determined regions of the E7 protein that were essential for its antiapoptotic activity. The ability of E7 to inhibit anoikis did partially correlate with an ability to enhance anchorage independence of BPV-1 E6-transformed cells. In addition, the antiapoptotic activity of E7 also only partially correlated with its ability to bind p600, a cellular protein that has previously been reported to play a role in anoikis. We conclude that the contribution of E7 to BPV-induced cellular transformation may involve its ability to inhibit anoikis but that additional functional activities must also be involved.
DeMasi
Joseph
J
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Chao
Michael C
MC
Kumar
Ashu S
AS
Howley
Peter M
PM
D019943:Amino Acid Substitution; D023102:Anoikis; D052688:Bovine papillomavirus 1 / Q000502:physiology*; D002472:Cell Transformation, Viral / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D009856:Oncogene Proteins, Viral; C075621:oncogene protein E7, Bovine papillomavirus type 1; C059269:protein E6, Bovine papillomavirus