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

Stable Identifier
R-HSA-112381
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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

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

Mol. Cell 2010
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of P-TEFb complex [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Created