Similarities and differences between the E5 oncoproteins of bovine papillomaviruses type 1 and type 4: cytoskeleton, motility and invasiveness in E5-transformed bovine and mouse cells.
Bovine papillomaviruses (BPVs) are oncogenic viruses. In cattle, BPV-1/2 is associated with urinary bladder cancer and BPV-4 with upper GI tract cancer. BPV E5 is a small hydrophobic protein localised in the endoplasmic reticulum (ER) and Golgi apparatus (GA). E5 is the major transforming protein of BPVs, capable of inducing cell transformation in cultured mouse fibroblasts and, in cooperation with E7, in primary bovine cells. E5-induced cell transformation is accompanied by activation of several cellular protein kinases, including growth factor receptors, and alkalinisation of endosomes and GA. We have reported that BPV E5 causes swelling and fragmentation of the GA and extensive vacuolisation of the cytoplasm. We now show that E5 from both BPV-1 and BPV-4 disturbs the actin cytoskeleton and focal adhesions in transformed bovine cells, where these morphological and behavioural characteristics are accompanied by hyperphosphorylation of the cellular phosphotyrosine kinase c-src. Both BPV-1 and BPV-4 E5 increase the motility of transformed mouse cells, but only BPV-1 E5 causes transformed mouse cells to penetrate a matrigel matrix. BPV-1 transformed mouse cells, but not BPV-4 transformed mouse cells, have hyperhpsphorylated c-src.
Tsirimonaki
Emmanuella
E
Institute of Comparative Medicine, University of Glasgow, Garscube Estate, Glasgow G61 1QH, Scotland, UK.
Ullah
Robina
R
Marchetti
Barbara
B
Ashrafi
G Hossein
GH
McGarry
Lynn
L
Ozanne
Brad
B
Campo
M Saveria
MS
D000199:Actins / Q000378:metabolism; D000818:Animals; D052688:Bovine papillomavirus 1 / Q000502:physiology*; D052697:Bovine papillomavirus 4; D000081247:CSK Tyrosine-Protein Kinase; D002417:Cattle; D002460:Cell Line; D002465:Cell Movement; D002472:Cell Transformation, Viral; D003599:Cytoskeleton / Q000648:ultrastructure*; D022001:Focal Adhesions / Q000648:ultrastructure*; D051379:Mice; D041681:NIH 3T3 Cells; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019061:src-Family Kinases
D000199:Actins; D009856:Oncogene Proteins, Viral; C054304:oncogene protein E5, Bovine papillomavirus type 1; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases