P-TEFb



Positive Transcription Elongation Factor b (P-TEFb) is the key factor regulating eukaryotic mRNA transcription at the level of elongation.

It is a cyclin dependent kinase, composed of Cdk9 and in humans one of three cyclins, T1, T2, or K.

The kinase activities of P-TEFb (the phosphorylation of serine 2 at RNA polymerase C-terminal repeats, the recruitment of TAT-SF1, a spliceosome recruiter, and the phosphorylation of hSPT5, a 5' capping enzyme recruiter ) is required to relieve RNA polymerase II from the negative elongation properties of DSIF and NELF and enter productive elongation resulting in mRNA production. pTEFb is regulated by the 7SK-RNA and HEXIM1 - when 7SK-RNA binds HEXIM1 it forms an inhibitor complex that inhibits pTEFb kinase activity.

P-TEFb is also a required cellular cofactor for HIV-Tat and inhibition of P-TEFb blocks HIV replication.