Phosphatidylinositol 3-Kinase/Akt pathway targets acetylation of Smad3 through Smad3/CREB-binding protein interaction. Contribution to transforming growth factor β1-induced Epstein-Barr virus reactivation

Epstein-Barr virus, a ubiquitous human herpesvirus, is associated with the development of carcinomas and lymphomas. We previously showed that transforming growth factor β1 (TGF-β1) 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-β1-induced ZEBRA expression and enabled Smad3, a mediator of TGF-β1 signaling, to be acetylated by direct interaction with the co-activator CREB-binding protein and then to regulate TGF-β1-induced ZEBRA expression. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.