Cellular localization of BARF1 oncoprotein and its cell stimulating activity in human epithelial cell

Emna Sakka, Axel zur Hausen, Karim Houali, Haying Liu, Sylvie Fiorini, Tadamasa Ooka*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)8-17
JournalVirus Research
Volume174
Issue number1-2
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Epstein-Barr virus
  • BARF1 protein
  • Human HaCaT epithelial cell
  • Nuclear localization
  • Mitogenic activity

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