Mechanisms controlling CDK9 activity.
This review primarily focuses on the mechanisms that modulate CDK9 activity and its recruitment to cellular genes, where it phosphorylates the C-terminal domain of RNA polymerase II (RNAPII) as well as negative elongation factors. CDK9 associates with each of four cyclins (T1, T2a, T2b and K), forming distinct positive transcription elongation factors (P-TEFb). Research done during the past decade has demonstrated a role for P-TEFb in stimulating elongation of otherwise paused RNAPII transcripts. Recent work suggests that P-TEFb also positively modulates other steps during transcription. In addition, "abnormal" CDK9 function is associated with certain diseases. Specifically, the activity of the cyclin T1/CDK9 complex is essential for HIV-1 replication and CDK9 upregulation is associated with cardiac hypertrophy. Thus, the role of CDK9 in these processes, and the possibility of therapeutically targeting CDK9, will also be briefly discussed.
Marshall
Renee M
RM
Fels Institute for Cancer Research and Molecular Biology, Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Grana
Xavier
X
D018797:Cell Cycle Proteins; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000502:physiology; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B / Q000502:physiology; D012313:RNA / Q000378:metabolism; D012319:RNA Polymerase II; D013601:T-Lymphocytes; D014157:Transcription Factors; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D042863:Cyclin-Dependent Kinase 9; D016213:Cyclins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D042925:Positive Transcriptional Elongation Factor B; D012313:RNA; D012319:RNA Polymerase II; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins