A human primary T-lymphocyte-derived human immunodeficiency virus type 1 Tat-associated kinase phosphorylates the C-terminal domain of RNA polymerase II and induces CAK activity.
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.
Mesh Terms:
CDC2-CDC28 Kinases, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases, Enzyme Activation, Gene Products, tat, HIV-1, Humans, Kinetics, Lymphocyte Activation, Phosphorylation, Positive Transcriptional Elongation Factor B, Protein Kinases, Protein-Serine-Threonine Kinases, RNA Polymerase II, Substrate Specificity, T-Lymphocytes, tat Gene Products, Human Immunodeficiency Virus
CDC2-CDC28 Kinases, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases, Enzyme Activation, Gene Products, tat, HIV-1, Humans, Kinetics, Lymphocyte Activation, Phosphorylation, Positive Transcriptional Elongation Factor B, Protein Kinases, Protein-Serine-Threonine Kinases, RNA Polymerase II, Substrate Specificity, T-Lymphocytes, tat Gene Products, Human Immunodeficiency Virus
J. Virol.
Date: Oct. 01, 1997
PubMed ID: 9311822
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