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

Helena S.Y. Mancebo; Gary Lee; John Flygare; Joanne Tomassini; Percy Luu; Yuerong Zhu; Junmin Peng; Carol Blau; Daria Hazuda; David Price; Osvaldo Flores

doi:10.1101/gad.11.20.2633

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

Journal article

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

Helena S.Y. Mancebo, Gary Lee, John Flygare, Joanne Tomassini, Percy Luu, Yuerong Zhu, Junmin Peng, Carol Blau, Daria Hazuda, David Price, …

Genes & development, Vol.11(20), pp.2633-2644

10/15/1997

DOI: 10.1101/gad.11.20.2633

PMCID: PMC316604

PMID: 9334326

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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.

HIV Tat protein

kinase inhibitors

P-TEFb kinase

Research Paper

transcriptional activation

Details

Title: Subtitle: P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro
Creators: Helena S.Y. Mancebo - Telik, Inc.
Gary Lee
John Flygare
Joanne Tomassini
Percy Luu
Yuerong Zhu
Junmin Peng
Carol Blau
Daria Hazuda
David Price
Osvaldo Flores
Resource Type: Journal article
Publication Details: Genes & development, Vol.11(20), pp.2633-2644
DOI: 10.1101/gad.11.20.2633
PMID: 9334326
PMCID: PMC316604
NLM abbreviation: Genes Dev
ISSN: 0890-9369
eISSN: 1549-5477
Publisher: Cold Spring Harbor Laboratory Press
Language: English
Date published: 10/15/1997
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9984288721502771

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