Article: article from journal or magazin.
Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4).
Molecular and Cellular Biology
The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.
Activating Transcription Factor 2, Activating Transcription Factor 4, Binding Sites, CREB-Binding Protein, Cyclic AMP Response Element-Binding Protein/genetics, Cyclic AMP Response Element-Binding Protein/metabolism, Fungal Proteins, Gene Products, tax/genetics, Gene Products, tax/metabolism, Human T-lymphotropic virus 1/genetics, Leucine Zippers, Mutagenesis, Nuclear Proteins/metabolism, Promoter Regions, Genetic, Protein Binding, Response Elements, Saccharomyces cerevisiae Proteins, T-Lymphocytes, Terminal Repeat Sequences, Trans-Activators/metabolism, Transcription Factors/genetics, Transcription Factors/metabolism, Transcriptional Activation
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