Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)
Copyright policy )Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)
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.
- French National Centre for Scientific Research France
- University of Queensland Australia
- University of Montpellier France
- Centre national de la recherche scientifique France
- University of Queensland Australia
570, Saccharomyces cerevisiae Proteins, Transcription Factor, T-Lymphocytes, Htlv-I Ltr, Gene-Expression, Long Terminal Repeat, Response Elements, Camp-Responsive Element, Activates Transcription, Fungal Proteins, [SDV.CAN] Life Sciences [q-bio]/Cancer, Element-Binding-Protein, Cyclic AMP Response Element-Binding Protein, Promoter Regions, Genetic, 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, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Human T-lymphotropic virus 1, Leucine Zippers, Binding Sites, Activating Transcription Factor 2, Cdna Clones, Terminal Repeat Sequences, Nuclear Proteins, Dna-Binding, Gene Products, tax, Leucine-Zipper Proteins, Activating Transcription Factor 4, CREB-Binding Protein, DNA-Binding Proteins, Mutagenesis, Trans-Activators, Protein Binding, Transcription Factors
570, Saccharomyces cerevisiae Proteins, Transcription Factor, T-Lymphocytes, Htlv-I Ltr, Gene-Expression, Long Terminal Repeat, Response Elements, Camp-Responsive Element, Activates Transcription, Fungal Proteins, [SDV.CAN] Life Sciences [q-bio]/Cancer, Element-Binding-Protein, Cyclic AMP Response Element-Binding Protein, Promoter Regions, Genetic, 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, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Human T-lymphotropic virus 1, Leucine Zippers, Binding Sites, Activating Transcription Factor 2, Cdna Clones, Terminal Repeat Sequences, Nuclear Proteins, Dna-Binding, Gene Products, tax, Leucine-Zipper Proteins, Activating Transcription Factor 4, CREB-Binding Protein, DNA-Binding Proteins, Mutagenesis, Trans-Activators, Protein Binding, Transcription Factors
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