Cap Binding Complex (CBC) P-TEFb complex DSIF:NELF:early elongation complex Early elongation complex with hyperphosphorylated Pol II CTD Hyperphosphorylation (Ser2) of RNA Pol II CTD by P-TEFb complex Authored: Gopinathrao, G, 2004-05-06 22:00:00 Cdk-9 is the kinase subunit of P-TEFb that phosphorylates Serine 2 on the heptapeptide repeats of Pol II CTD alleviating the negative action of DSIF-NELF complex. This reaction is considered to be a rate limiting step for processive elongation. P-TEFb complex, that has a DRB-sensitive cyclin-dependent kinase activity, is composed of ~43 kDa, Cdk9 kinase (PITALRE), and either Cyclin T1, Cyclin T2a, Cyclin T2b, or Cyclin K. The exact mechanism by which P-TEFb removes the inhibition of elongation by DSIF-NELF is not yet known. P-TEFb is also capable of phosphorylating Spt5 subunit of DSIF complex. <BR> A P-TEFb complex (which contains only the Cyclin T1) is implicated in the efficient synthesis of human immunodeficiency virus-1 (HIV-1) transcripts. Cyclin T1 subunit of the P-TEFb(Cyclin T1:Cdk9) complex interacts with HIV-1 encoded Tat protein that binds to the transactivation response (TAR) element in the nascent HIV-1 transcript (reviewed in Price,2000). <BR>The mechanism by which DSIF, NELF and P-TEFb or TAK/P-TEFb act together in Pol II-regulated elongation is yet to be fully understood. Various biochemical evidences point to a model in which DSIF and NELF negatively regulate elongation through interactions with polymerase containing a hypophosphorylated CTD. Subsequent phosphorylation of the Pol II CTD by P-TEFb might promote elongation by inhibiting interactions of DSIF and NELF with the elongation complex.<BR> Pubmed10733565 Pubmed9857195 Reactome Database ID Release 43112381 Reactome, http://www.reactome.org ReactomeREACT_2066