THE BOVINE PAPILLOMAVIRUS E6 PROTEIN BINDS TO THE LD MOTIF REPEATS OFPAXILLIN AND BLOCKS ITS INTERACTION WITH VINCULIN AND THE FOCAL ADHESION KINASE

The bovine papillomavirus type 1 (BPV-1) E6 oncoprotein can transform fibroblasts and induce anchorage-independent growth and disassembly of the actin stress fibers, We have previously shown that the E6 protein interacts with the focal adhesion protein, paxillin, suggesting a dir ect role of E6 in the disruption of the actin cytoskeleton. We have no w mapped the E6 binding sites on paxillin to the LD motif repeats regi on, which has been implicated in mediating paxillin binding to two oth er focal adhesion proteins, vinculin and the focal adhesion kinase. Th e five LD motif repeats identified in paxillin do not contribute equal ly to its interaction with E6. The first LD repeat is most critical fo r paxillin binding to E6 both in vitro and in vivo. Furthermore, the b inding of recombinant wild-type E6 protein to paxillin blocked the int eraction of several cellular proteins with paxillin, including vinculi n and the focal adhesion kinase, A mutant E6 protein (H105) which does not bind to paxillin had no effect on the binding of these cellular p roteins to paxillin, These data suggest that E6 disruption of the acti n stress fibers occurs through blocking the interaction of paxillin wi th its cellular effecters such as vinculin and the focal adhesion kina se.