title: Cellular localization of BARF1 oncoprotein and its cell stimulating activity in human epithelial cell.
abstract: BARF1 gene encoded by Epstein-Barr virus is capable of immortalizing the primary monkey epithelial cells and of inducing malignant transformation in human EBV-negative B cell lines as well as rodent fibroblast. This oncoprotein is a secreted protein capable of acting as a powerful mitogen. We have studied the effect of BARF1 protein in transfected or BARF1 protein treated human HaCaT epithelial cells. In BARF1-transfected cells, cell growth was activated and its protein was found both in culture medium and cellular compartment (membrane, cytoplasm and nuclei). When purified BARF1 protein was exogenously added in the cell culture medium of HaCaT cells in absence of fetal calf serum led to its entrance into cells and its intracellular localization in cytoplasm, nuclear periphery and nuclei at 14h treatment, determined by confocal and immunoelectron microscopy. Cell fractionation confirmed its nuclear localization. Nuclear localization was observed in both systems. More interestingly, purified BARF1 protein p29 exogenously added in the cell culture medium activated cell passage of G1 to S phase. S phase activation by its autocrine activity and its tumorigenic activity would be associated with the development of EBV-associated carcinomas.
authors: Laboratoire de Virologie Moléculaire, FRE3011, CNRS, Faculté de Médecine Laennec, Université Claude Bernard Lyon-1, 69372 Lyon, France.
authors: Emna
authors: E
authors: Sakka
authors: Axel
authors: A
authors: Zur Hausen
authors: Karim
authors: K
authors: Houali
authors: Haying
authors: H
authors: Liu
authors: Sylvie
authors: S
authors: Fiorini
authors: Tadamasa
authors: T
authors: Ooka
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D049109:Cell Proliferation; D003593:Cytoplasm / Q000737:chemistry; D004847:Epithelial Cells / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D018613:Microscopy, Confocal; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C086495:BARF1 protein, Human herpesvirus 4; D014764:Viral Proteins