P-TEFb

RNA Polymerase II Elongation Control. RNA polymerase II comes under the control of negative elongation factors (DSIF^[1] and NELF^[2]) shortly after initiation. P-TEFb mediates a transition into productive elongation by phosphorylating the CTD of the large subunit of RNA polymerase II and DSIF

Positive Transcription Elongation Factor b (P-TEFb) is the key factor regulating eukaryotic mRNA transcription at the level of elongation^[3][4].

It is a cyclin dependent kinase, composed of Cdk9 and in humans one of three cyclins, T1, T2, or K^[5].

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^[6]) is required to relieve RNA polymerase II from the negative elongation properties of DSIF and NELF and enter productive elongation resulting in mRNA production^[7]. pTEFb is regulated by the 7SK-RNA and HEXIM1 - when 7SK-RNA binds HEXIM1 it forms an inhibitor complex that inhibits pTEFb kinase activity ^[8].

P-TEFb is also a required cellular cofactor for HIV-Tat^[9] and inhibition of P-TEFb blocks HIV replication^[10].

References

1. ^ Wada, T., Takagi, T., Yamaguchi, Y., Ferdous, A., Imai, T., Hirose, S., Sugimoto, S., Yano, K., Hartzog, G.A., Winston, F., et al. (1998). DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes & development 12, 343-356.
2. ^ Yamaguchi, Y., Takagi, T., Wada, T., Yano, K., Furuya, A., Sugimoto, S., Hasegawa, J., and Handa, H. (1999). NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 97, 41-51.
3. ^ Marshall, N.F. and Price, D.H. (1995) "Purification of P-TEFb, a transcription factor required for the transition into productive elongation." J. Biol. Chem. Communication 270:12335-12338.
4. ^ Marshall, N.F., Peng, J., Xie, Z., and Price, D.H. (1996) Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. J. Biol. Chem. 271:27176.
5. ^ Peng, J., Zhu, Y., Milton, J.T., and Price, D.H. (1998) Identification of multiple cyclin subunits of human P-TEFb. Genes and Development 12:755-762.
6. ^ Watson et al., Molecular Biology of the Gene, 5th ed., Benjamin Cummings p.371
7. ^ Peterlin, B.M, Price, D.H (2006) Controlling the elongation phase of transcription with P-TEFb Molecular Cell 23:297-305.
8. ^ Modulation of a P-TEFb Functional Equilibrium for the Global Control of Cell Growth and Differentiation - Mol Cell Biol. 2006 October; 26(19): 7068–7076
9. ^ Zhu, Y., Pe’ery, T., Peng, J., Ramanathan, Y., Marshall, N.F., Marshall, T.K., Amendt, B.A., Mathews, M.B., Price, D.H. (1997) Transcription elongation factor P-TEFb is required for HIV-1 Tat transactivation in vitro. Genes and Development 11:2622-2632.
10. ^ Chao, S-H., Price, D.H. (2001) "Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo." J. Biol. Chem. 276:31793-31799.

External links

• MeSH Positive+Transcriptional+Elongation+Factor+B