The ability of positive transcription elongation factor B to transactivate human immunodeficiency virus transcription depends on a functional kinase domain, cyclin T1, and Tat.
By binding to the transactivation response element (TAR) RNA, the transcriptional transactivator (Tat) from the human immunodeficiency virus increases rates of elongation rather than initiation of viral transcription. Two cyclin-dependent serine/threonine kinases, CDK7 and CDK9, which phosphorylate the C-terminal domain of RNA polymerase II, have been implicated in Tat transactivation in vivo and in vitro. In this report, we demonstrate that CDK9, which is the kinase component of the positive transcription elongation factor b (P-TEFb) complex, can activate viral transcription when tethered to the heterologous Rev response element RNA via the regulator of expression of virion proteins (Rev). The kinase activity of CDK9 and cyclin T1 is essential for these effects. Moreover, P-TEFb binds to TAR only in the presence of Tat. We conclude that Tat-P-TEFb complexes bind to TAR, where CDK9 modifies RNA polymerase II for the efficient copying of the viral genome.
Departments of Medicine, Microbiology, and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143-0703, USA.
K
K
Fujinaga
T P
TP
Cujec
J
J
Peng
J
J
Garriga
D H
DH
Price
X
X
Graña
B M
BM
Peterlin
D002461:Cell Line, Transformed; D056906:Cyclin T; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D015694:Gene Products, rev / Q000235:genetics; D015696:Gene Products, tat / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D010445:Peptide Elongation Factors / Q000378:metabolism*; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D015694:Gene Products, rev; D015696:Gene Products, tat; D010445:Peptide Elongation Factors; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases