The Epstein Barr nuclear antigen EBNA3C regulates transcription, cell transformation and cell migration.

Abstract

The Epstein-Barr virus (EBV) infects most of the human population and persists in B-lymphocytes for the lifetime of the host. During the establishment of latent infection a unique repertoire of genes are expressed. The EBV nuclear antigen EBNA3C is essential for growth transformation of primary B-lymphocytes in vitro. EBNA3C regulates the transcription of a number of viral and cellular genes important for the immortalization process. Interaction of EBNA3C with the cellular transcription factor RBP-Jkappa and HDAC1 modulates transcriptional activation. Additionally, EBNA3C disrupts the cyclin/cdk-Rb-E2F pathway that regulates cell cycle progression through the restriction point at G1. Recent studies showed that the carboxy terminal region of EBNA3C from aa 366-992, essential for the immortalization of primary B-cells, interacts with Prothymosin(alpha) (ProTalpha) and Nm23-H1. The interaction of EBNA3C with ProTalpha as well as the histone acetylase p300 suggested a possible role in modulation of histone acetylation and chromatin remodeling. Cell migration assays geared towards determining the effect of EBNA3C on Nm23-H1 antimetastatic function suggests that EBNA3C suppresses the effects of NM23-H1 on the motility of breast carcinoma as well as Burkitt's lymphoma cells. This observation suggests that EBNA3C may be involved in driving the metastatic process in EBV associated human malignancies.