Figure 1.

CDK9 function in RNA Pol II activation and gene transcription: (A) CDK9 associates with cyclin T1 (CycT1) forming the positive transcription elongation factor b (P-TEFb) complex. The P-TEFb complex is inactive when incorporated into the 7SK small nuclear ribonucleoprotein complex (snRNP) which includes HEXIM. LARP7 interacts with 7SKsnRNP to increase complex stability. RNA polymerase II (RNA PolII) is loaded with the negative elongation factors negative elongation factor (NELF) and DRB sensitivity-inducing factor (DSIF), blocking transcription elongation. (B) Upon transcriptional stimuli, CDK9 release factors (CDK9 RF) post-translationally modifies the 7SKsnRNP/P-TEFb complex to promote the release of P-TEFb. To this process concurs the activation/phosphorylation of CDK9 by CDK7, which works as a CDK activating kinase (CAK). Active P-TEFb complex, in turn, phosphorylates DSIF and NELF and the Ser2 of the RNA PolII C terminal domain (CTD) at target promoters to remove elongation blocks. (C) Bromodomain protein 4 (BRD4), which is recruited by transcription factors on promoters of target genes that must be activated, recruits, in turn, activated P-TEFb and super elongation complex (SEC) allowing transcriptional elongation and expression of target genes.