P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro

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Abstract

To identify novel inhibitors of transcriptional activation by the HIV Tat protein, we used a combination of in vitro and in vivo Tat-dependent transcription assays to screen >100,000 compounds. All compounds identified blocked Tat-dependent stimulation of transcriptional elongation. Analysis of a panel of structurally diverse inhibitors indicated that their target is the human homolog of Drosophila positive transcription elongation factor b (P- TEFb). Loss of Tat transactivation in extracts depleted of the kinase subunit of human P-TEFb, PITALRE, was reversed by addition of partially purified human P-TEFb. Transfection experiments with wild-type or kinase knockout PITALRE demonstrated that P-TEFb is required for Tat function. Our results suggest that P-TEFb represents an attractive target for the development of novel HIV therapeutics.

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Mancebo, H. S. Y., Lee, G., Flygare, J., Tomassini, J., Luu, P., Zhu, Y., … Flores, O. (1997). P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro. Genes and Development, 11(20), 2633–2644. https://doi.org/10.1101/gad.11.20.2633

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