Analysis of CREB mutants in Tax complex formation and trans-activation

The human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax interacts w ith cellular transcription factors to facilitate viral replication in infec ted cells. Tax binds to the cellular transcription factor CREB and the cell ular coactivator protein CBP to form a stable nucleoprotein complex on the viral enhancer elements. The formation of this complex is believed to promo te strong Tax-dependent transcriptional activation of viral gene expression . In this study, we characterize a series of internal CREB deletion mutants with respect to Tax and CBP recruitment and transcriptional activation. We find that, although several of these mutants are unable to support ternary complex formation with Tax and the viral CRE DNA, they are fully competent for cooperation with Tax in CBP recruitment. Unexpectedly, CREB proteins t hat carry deletions in a carboxy-terminal region of the KID domain, while c ompetent for ternary and quaternary complex formation, were defective for T ax trails-activation in vivo. These studies suggest that CREB may serve mor e than just a "scaffolding" role in Tax trans-activation, cooperating direc tly with Tax (and CBP) to mediate strong transcriptional activation of the provirus.