Hyperphosphorylation (Ser2) of RNA Pol II CTD by P-TEFb complex

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
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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.
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).
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.
Literature References
PubMed ID Title Journal Year
20159561 AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia

Smith, ER, Martin-Brown, S, Lin, C, Takahashi, H, Conaway, RC, Florens, LA, Lai, KC, Shilatifard, A, Conaway, JW, Washburn, MP

Mol. Cell 2010
Catalyst Activity

protein serine/threonine kinase activity of P-TEFb complex [nucleoplasm]

Orthologous Events
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