Phosphatidylinositol 3-Kinase/Akt Pathway Targets Acetylation of Smad3 through Smad3/CREB-binding Protein Interaction: Contribution to transforming growth factor 1-induced epstein-barr virus reactivation

Abstract

Epstein-Barr virus, a ubiquitous human herpesvirus, is associated with the development of carcinomas and lymphomas. We previously showed that transforming growth factor 1 (TGF- 1) mediated the virus to enter the lytic cycle, which is triggered by expression of Z Epstein-Barr virus replication activator (ZEBRA), through the ERK 1/2 MAPK signaling pathway. We report here that Akt, activated downstream from ERK 1/2, was required for TGF- 1-induced ZEBRA expression and enabled Smad3, a mediator of TGF- 1 signaling, to be acetylated by direct interaction with the co-activator CREB-binding protein and then to regulate TGF- 1-induced ZEBRA expression.