Upregulation of cyclin T1/CDK9 complexes during T cell activation (original) (raw)

Oncogene volume 17, pages 3093–3102 (1998)Cite this article

Abstract

Cyclin T1 has been identified recently as a regulatory subunit of CDK9 and as a component of the transcription elongation factor P-TEFb. Cyclin T1/CDK9 complexes phosphorylate the carboxy terminal domain (CTD) of RNA polymerase II (RNAP II) in vitro. Here we report that the levels of cyclin T1 are dramatically upregulated by two independent signaling pathways triggered respectively by PMA and PHA in primary human peripheral blood lymphocytes (PBLs). Activation of these two pathways in tandem is sufficient for PBLs to enter and progress through the cell cycle. However, the expression of cyclin T1 is not growth and/or cell cycle regulated in other cell types, indicating that regulation of cyclin T1 expression is dependent on tissue-specific signaling pathways. Upregulation of cyclin T1 in stimulated PBLs results in induction of the CTD kinase activity of the cyclin T1/CDK9 complex, which in turn correlates directly with phosphorylation of RNAP II in vivo, linking for the first time activation of the cyclin T1/CDK9 pair with phosphorylation of RNAP II in vivo. In addition, we report here that endogenous CDK9 and cyclin T1 complexes associate with HIV-1 generated Tat in relevant cells and under physiological conditions (HIV-1 infected T cells). This, together with our results showing that HIV-1 replication in stimulated PBLs correlates with the levels of cyclin T1 protein and associated CTD kinase activity, suggests that the cyclin T1/CDK9 pair is one of the HIV-1 required host cellular cofactors generated during T cell activation.

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Authors and Affiliations

  1. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, 19140, Pennsylvania, USA
    Judit Garriga, Matilde Parreño, Earl E Henderson & Xavier Graña
  2. Department of Biochemistry, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, 19140, Pennsylvania, USA
    Judit Garriga, Matilde Parreño & Xavier Graña
  3. Microbiology and Immunology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, 19140, Pennsylvania, USA
    Earl E Henderson
  4. Department of Biochemistry, University of Iowa, Iowa City, 52242, Iowa, USA
    Junmin Peng & David H Price

Authors

  1. Judit Garriga
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  2. Junmin Peng
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  3. Matilde Parreño
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  4. David H Price
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  5. Earl E Henderson
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  6. Xavier Graña
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Garriga, J., Peng, J., Parreño, M. et al. Upregulation of cyclin T1/CDK9 complexes during T cell activation.Oncogene 17, 3093–3102 (1998). https://doi.org/10.1038/sj.onc.1202548

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