P-TEFb
Encyclopedia
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 cyclin
s, 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.
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
mRNA transcription at the level of elongation.
It is a cyclin dependent kinase, composed of Cdk9
CDK9
CDK9 or cyclin-dependent kinase 9 is a cyclin-dependent kinase associated with P-TEFb.CDK9 is also known to associate with other proteins such as TRAF2, and be involved in differentiation of skeletal muscle...
and in humans one of three cyclin
Cyclin
Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase enzymes.- Function :...
s, 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
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
from the negative elongation properties of DSIF
DSIF
DSIF is a factor that can either negatively or positively affect transcription by RNA polymerase II . In one case of negative regulation, it can interact with NELF to promote the stalling of Pol II at some genes. This stalling is released by P-TEFb. In humans, DSIF is composed of hSPT4 and...
and NELF
Negative elongation factor
NELF is a four subunit protein that affects transcription by RNA polymerase II. Subunit NELF-E is also known as RDBP. The NELF-A subunit is encoded by the gene WHSC2, Wolf-Hirschhorn syndrome candidate 2...
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.