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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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.[1]

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