P-TEFb complex binding

Definition

Target type: molecularfunction

Binding to a P-TEFb complex. [GOC:pga, PMID:18391197]

P-TEFb, a critical regulator of transcription elongation, exerts its influence by binding to and phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). This interaction is crucial for facilitating the transition from transcription initiation to elongation. The P-TEFb complex comprises two subunits: cyclin-dependent kinase 9 (CDK9) and cyclin T1 or cyclin T2. CDK9, a serine/threonine kinase, possesses the catalytic activity responsible for phosphorylating the CTD. The CTD of RNAPII is a highly conserved, repetitive sequence consisting of heptapeptide repeats with the consensus sequence YSPTSPS. P-TEFb specifically targets Serine 2 (Ser2) within these repeats, leading to its phosphorylation. Phosphorylation of Ser2 on the CTD serves as a molecular switch, triggering a cascade of events that promote elongation. Notably, the recruitment of P-TEFb to the transcription machinery is tightly regulated. It is believed that P-TEFb exists in an inactive state within the cell, bound to the 7SK snRNP complex. Upon receiving signals, such as the presence of paused RNAPII or the activation of signaling pathways, P-TEFb is released from the 7SK snRNP complex and becomes available for recruitment to the transcription site. The precise mechanism of P-TEFb recruitment varies depending on the specific gene and regulatory context. Once recruited to the transcription site, P-TEFb phosphorylates Ser2 on the CTD of RNAPII, facilitating the transition from initiation to elongation. This phosphorylation event triggers several downstream effects, including: (1) recruitment of elongation factors, such as SII and TFIIS, which enhance the processivity of RNAPII; (2) dissociation of negative elongation factors (NELFs), which hinder elongation; (3) recruitment of splicing factors, facilitating the removal of introns from the nascent RNA transcript; (4) recruitment of polyadenylation factors, initiating the process of mRNA 3'-end processing. In summary, P-TEFb binding and its associated Ser2 phosphorylation of the CTD play a pivotal role in regulating transcription elongation, ensuring efficient and accurate production of mRNA molecules.'
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Proteins (1)

Compounds (45)