P-TEFb

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RNA Polymerase II Elongation Control. RNA polymerase II comes under the control of negative elongation factors (DSIF and NELF) 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
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, comprised 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].

P-TEFb is also a required cellular cofactor for HIV-Tat[8] and inhibition of P-TEFb blocks HIV replication[9].

[edit] 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. ^ 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.
  9. ^ 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.

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