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TFIIH Inhibits CDK9 Phosphorylation during Human Immunodeficiency Virus Type 1 Transcription
Journal article   Open access   Peer reviewed

TFIIH Inhibits CDK9 Phosphorylation during Human Immunodeficiency Virus Type 1 Transcription

Meisheng Zhou, Sergei Nekhai, Diana C Bharucha, Ajit Kumar, Hui Ge, David H Price, Jean-Marc Egly and John N Brady
The Journal of biological chemistry, Vol.276(48), pp.44633-44640
11/30/2001
DOI: 10.1074/jbc.M107466200
PMID: 11572868
url
https://doi.org/10.1074/jbc.M107466200View
Published (Version of record) Open Access

Abstract

Tat stimulates human immunodeficiency virus, type 1 (HIV-1), transcription elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of CDK9 and cyclin T1, to the TAR RNA structure. It has been demonstrated further that CDK9 phosphorylation is required for high affinity binding of Tat/P-TEFb to the TAR RNA structure and that the state of P-TEFb phosphorylation may regulate Tat transactivation. We now demonstrate that CDK9 phosphorylation is uniquely regulated in the HIV-1 preinitiation and elongation complexes. The presence of TFIIH in the HIV-1 preinitiation complex inhibits CDK9 phosphorylation. As TFIIH is released from the elongation complex between +14 and +36, CDK9 phosphorylation is observed. In contrast to the activity in the "soluble" complex, phosphorylation of CDK9 is increased by the presence of Tat in the transcription complexes. Consistent with these observations, we have demonstrated that purified TFIIH directly inhibits CDK9 autophosphorylation. By using recombinant TFIIH subcomplexes, our results suggest that the XPB subunit of TFIIH is responsible for this inhibition of CDK9 phosphorylation. Interestingly, our results further suggest that the phosphorylated form of CDK9 is the active kinase for RNA polymerase II carboxyl-terminal domain phosphorylation.

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