The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton.
The E6 oncoprotein of bovine papillomavirus type 1 (BPV-1) has been shown to transform cells through a p53-independent pathway, but its transforming mechanism is unknown. Here we demonstrate in vitro and in vivo interactions between BPV-1 E6 and the focal adhesion protein paxillin. The ability of BPV-1 E6 to complex with paxillin correlated with its ability to transform; E6 mutant proteins impaired in their transformation function also were impaired in their abilities to bind paxillin. E6 binding to paxillin also may contribute to the carcinogenic potential of the human papillomavirus (HPV); we were able to show in vitro binding of paxillin to the E6 proteins of the cancer-associated type HPV 16 but not of the nononcogenic types 6 and 11. The association of E6 with paxillin was affected by depolymerization of the actin fiber network, and overexpression of BPV-1 E6 led to disruption of actin fiber formation. Disruption of the actin cytoskeleton is a characteristic of many transformed cells, and, in BPV-1 transformed cells, may be mediated by BPV-1 E6 through its interaction with paxillin.
Tong
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Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Howley
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PM
D000199:Actins / Q000502:physiology; D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008856:Microscopy, Fluorescence; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D009856:Oncogene Proteins, Viral; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; C059269:protein E6, Bovine papillomavirus; D015638:Cytochalasin D