9311822

pubmed:Citation

10

Tat protein mediates transactivation of human immunodeficiency virus type 1 (HIV-1), which results in more-efficient transcript elongation. Since phosphorylation of C-terminal domain (CTD) of RNA polymerase II correlates with its enhanced processivity, we studied the properties of a Tat-associated CTD kinase derived from mitogenically stimulated human primary T lymphocytes (TTK). TTK binds to full-length Tat and specifically phosphorylates CTD and CDK2. This dual kinase activity is characteristic of CDK-activating kinase (CAK). The CTD kinase activity is induced upon mitogenic stimulation of primary T lymphocytes. Fractionation of T-cell lysate demonstrates that Tat-associated CTD kinase activity elutes in two peaks. About 60% of Tat-associated CTD kinase copurifies with CDK2 kinase activity and contains the CAK components CDK7 and cyclin H. The rest of Tat-associated kinase is free of CDK2 kinase activity and the CAK components and thus may represent a novel CTD kinase. The kinase activities of TTK are blocked by the adenosine analog 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB) as well as by the kinase inhibitor H8 at concentrations known to block transcript elongation. Importantly, the Tat-associated kinase markedly induced CAK. We suggest that the mechanism of Tat-mediated processive transcription of the HIV-1 promoter includes a Tat-associated CAK activator.

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http://linkedlifedata.com/resource/pubmed/journal/0113724

http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases, http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat, http://linkedlifedata.com/resource/pubmed/chemical/Positive Transcriptional..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA Polymerase II, http://linkedlifedata.com/resource/pubmed/chemical/carboxy-terminal domain kinase, http://linkedlifedata.com/resource/pubmed/chemical/cyclin-dependent kinase-activating..., http://linkedlifedata.com/resource/pubmed/chemical/tat Gene Products, Human...

Oct

pubmed-author:KumarAA, pubmed-author:NekhaiSS, pubmed-author:ShuklaR RRR

71

Y

2009-11-19