Positive transcription elongation factor b (P-TEFb) (P-TEFb)

Positive transcription elongation factor b (P-TEFb) is a critical heterodimeric protein kinase complex composed of Cyclin-dependent kinase 9 (CDK9) and its regulatory partner, typically Cyclin T1 (Source: UniProt P50750, O60563). It serves as a master regulator of the eukaryotic transcription cycle by facilitating the transition of RNA polymerase II from promoter-proximal pausing to active elongation (Source: Zhou et al., 2012, PMID: 22658488). This transition is mediated by the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II at Serine 2, as well as the phosphorylation of negative elongation factors such as DSIF and NELF (Source: Bacon and D'Orso, 2019, PMID: 30718361). In oncology, P-TEFb is frequently dysregulated, driving the expression of key oncogenes and anti-apoptotic proteins like MYC and MCL-1, which are characterized by short mRNA half-lives and high dependence on continuous transcription (Source: Wang et al., 2014, PMID: 24513106). Additionally, P-TEFb is a mandatory host factor for HIV-1 replication, where the viral Tat protein recruits the complex to the viral promoter to ensure efficient transcription of the viral genome (Source: Wei et al., 1998, PMID: 9465039). Therapeutic targeting of P-TEFb primarily involves small-molecule inhibitors of the CDK9 subunit, with several selective agents currently in clinical trials for hematologic malignancies and solid tumors (Source: ClinicalTrials.gov, NCT03263637).

Other names

CDK9-Cyclin T complexCDK9-CCNT1 complexTranscriptional CDK complex P-TEFbCyclin-dependent kinase 9 complex

Inhibition of the catalytic subunit CDK9, preventing phosphorylation of RNA polymerase II C-terminal domain (CTD) at Serine 2, as well as phosphorylation of negative elongation factors DSIF and NELF, leading to the arrest of transcriptional elongation and subsequent downregulation of short-lived oncogenic proteins (Source: Bacon and D'Orso, 2019, PMID: 30718361).