Molecular recognition of the human coactivator CBP by the HIV-1 transcriptional activator Tat.

HIV-1 Tat is required for the expression of the viral genome. Tat binds to an RNA stem-loop and mediates the recruitment of human coactivators to facilitate HIV-1 transcription. The coactivator and acetyltransferase CREB binding protein (CBP), and the paralog p300, are recruited to the HIV-1 promoter by Tat. Here we ...
identify the interacting domains of Tat and CBP. Circular dichroism and pulldown assays show that full-length Tat binds to the KIX domain of CBP, but not to the C/H1 or CR2 domains. Circular dichroism and NMR studies of Tat deletion mutants localize the KIX-binding domain of Tat to the N-terminal 24 residues of Tat. Transient cotransfections demonstrate that exogenous KIX behaves as a dominant negative to Tat-mediated transcription in human T-cells, suggesting that Tat and KIX interact in vivo. These findings indicate that Tat targets the KIX domain of CBP and provide insight into the molecular interactions involved in regulating HIV-1 gene expression.
Mesh Terms:
Amino Acid Sequence, Animals, CREB-Binding Protein, Circular Dichroism, Cyclic AMP Response Element-Binding Protein, DNA-Binding Proteins, E1A-Associated p300 Protein, Gene Products, tat, HIV-1, Humans, Jurkat Cells, Kinesin, Mice, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Recombinant Fusion Proteins, T-Lymphocytes, Trans-Activators, Transcriptional Activation, tat Gene Products, Human Immunodeficiency Virus
Date: Feb. 04, 2003
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