Positive Transcription Elongation Factor b (P-TEFb)

Positive transcription elongation factor b (P-TEFb) is a multiprotein complex that plays an essential role in the regulation of gene expression by facilitating the transition of RNA polymerase II (Pol II) from promoter-proximal pausing to productive elongation during transcription in eukaryotic cells. P-TEFb consists primarily of two subunits: cyclin-dependent kinase 9 (CDK9) and a regulatory cyclin (T1, T2, or K). P-TEFb phosphorylates the CTD of RNA polymerase II and negative elongation factors, releasing Pol II from pausing. It is negatively regulated by HEXIM proteins and positively by BRD4 and the super elongation complex. P-TEFb is essential for general gene expression, plays a specific role in muscle cell development, and contributes to inflammatory diseases and cancer. HIV exploits P-TEFb for efficient replication. P-TEFb inhibitors are under investigation for cancer therapy.

CDK9 kinase inhibition