Abstract:
The Tax protein of human T-lymphotropic virus (HTLV)-1 activates expression of the HTLV-1 long terminal repeat through a DNA element that resembles the cellular cyclic AMP-regulated enhancer (CRE). Tax contains a transcriptional activation domain, but its ability to activate gene expression depends on interactions with cellular CRE-binding proteins such as CREB. Whether Tax can activate the expression of cellular CRE-containing genes has been controversial. Here we show that Tax can activate both the HTLV-1 and consensus cellular CREs, and propose that this activation may occur through mechanisms that are differentially dependent on CREB phosphorylation. Tax not only increases the binding of CREB to the viral CRE but also recruits the transcriptional co-activator CBP in a manner independent of CREB phosphorylation. In contrast, association of Tax with the cellular CRE occurs through CBP which, in turn, is recruited only in the presence of phosphorylated CREB.
Keywords: Base Sequence Binding Sites Cloning, Molecular Cyclic AMP/METABOLISM Cyclic AMP-Dependent Protein Kinases/METABOLISM DNA/METABOLISM DNA-Binding Protein, Cyclic AMP-Responsive/*METABOLISM DNA, Viral/METABOLISM *Enhancer Elements (Genetics) Fluorescence Polarization *Gene Expression Regulation, Viral Gene Products, tax/*METABOLISM Genes, Reporter Human HTLV-I/*GENETICS Molecular Sequence Data Nuclear Proteins/METABOLISM Phosphorylation Protein Binding Recombinant Fusion Proteins/METABOLISM Saccharomyces cerevisiae Somatostatin/GENETICS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors/METABOLISM Tumor Cells, Cultured JOURNAL ARTICLE 960730
M9670424
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