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Volume 271, Number 43, Issue of October 25, 1996 pp. 27176-27183
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

Control of RNA Polymerase II Elongation Potential by a Novel Carboxyl-terminal Domain Kinase

(Received for publication, June 5, 1996, and in revised form, July 19, 1996)

Nick F. Marshall , Junmin Peng , Zhi Xie and David H. Price

From the Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242

The entry of RNA polymerase II into a productive mode of elongation is controlled, in part, by the postinitiation activity of positive transcription elongation factor b (P-TEFb) (Marshall, N. F., and Price, D. H. (1995) J. Biol. Chem. 270, 12335-12338). We report here that removal of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II abolishes productive elongation. Correspondingly, we found that P-TEFb can phosphorylate the CTD of pure RNA polymerase II. Furthermore, P-TEFb can phosphorylate the CTD of RNA polymerase II when the polymerase is in an early elongation complex. Both the function and kinase activity of P-TEFb are blocked by the drugs 5,6-dichloro-1-beta -D-ribofuranosylbenzimidazole (DRB) and H-8. P-TEFb is distinct from transcription factor IIH (TFIIH) because the two factors have no subunits in common, P-TEFb is more sensitive to DRB than is TFIIH, and most importantly, TFIIH cannot substitute functionally for P-TEFb. We propose that phosphorylation of the CTD by P-TEFb controls the transition from abortive into productive elongation mode.


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M. Kimura, H. Suzuki, and A. Ishihama
Formation of a Carboxy-Terminal Domain Phosphatase (Fcp1)/TFIIF/RNA Polymerase II (pol II) Complex in Schizosaccharomyces pombe Involves Direct Interaction between Fcp1 and the Rpb4 Subunit of pol II
Mol. Cell. Biol., March 1, 2002; 22(5): 1577 - 1588.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
M. Hoque, T. M. Young, C.-G. Lee, G. Serrero, M. B. Mathews, and T. Pe'ery
The Growth Factor Granulin Interacts with Cyclin T1 and Modulates P-TEFb-Dependent Transcription
Mol. Cell. Biol., March 1, 2002; 23(5): 1688 - 1702.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
J. Martin-Serrano, K. Li, and P. D. Bieniasz
Cyclin T1 Expression Is Mediated by a Complex and Constitutively Active Promoter and Does Not Limit Human Immunodeficiency Virus Type 1 Tat Function in Unstimulated Primary Lymphocytes
J. Virol., January 1, 2002; 76(1): 208 - 219.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
S. R. Eberhardy and P. J. Farnham
c-Myc Mediates Activation of the cad Promoter via a Post-RNA Polymerase II Recruitment Mechanism
J. Biol. Chem., December 14, 2001; 276(51): 48562 - 48571.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
R. E. Kiernan, S. Emiliani, K. Nakayama, A. Castro, J. C. Labbe, T. Lorca, K.-i. Nakayama, and M. Benkirane
Interaction between Cyclin T1 and SCFSKP2 Targets CDK9 for Ubiquitination and Degradation by the Proteasome
Mol. Cell. Biol., December 1, 2001; 21(23): 7956 - 7970.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
D. B. Renner, Y. Yamaguchi, T. Wada, H. Handa, and D. H. Price
A Highly Purified RNA Polymerase II Elongation Control System
J. Biol. Chem., November 2, 2001; 276(45): 42601 - 42609.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
H. L. Jenkins and C. A. Spencer
RNA Polymerase II Holoenzyme Modifications Accompany Transcription Reprogramming in Herpes Simplex Virus Type 1-Infected Cells
J. Virol., October 15, 2001; 75(20): 9872 - 9884.
[Abstract] [Full Text] [PDF]


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Mol. Pharmacol.Home page
M. Ljungman and M. T. Paulsen
The Cyclin-Dependent Kinase Inhibitor Roscovitine Inhibits RNA Synthesis and Triggers Nuclear Accumulation of p53 That Is Unmodified at Ser15 and Lys382
Mol. Pharmacol., October 1, 2001; 60(4): 785 - 789.
[Abstract] [Full Text] [PDF]


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GeneticsHome page
D. L. Lindstrom and G. A. Hartzog
Genetic Interactions of Spt4-Spt5 and TFIIS With the RNA Polymerase II CTD and CTD Modifying Enzymes in Saccharomyces cerevisiae
Genetics, October 1, 2001; 159(2): 487 - 497.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
P. Licciardo, L. Ruggiero, L. Lania, and B. Majello
Transcription activation by targeted recruitment of the RNA polymerase II CTD phosphatase FCP1
Nucleic Acids Res., September 1, 2001; 29(17): 3539 - 3545.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
S. Murray, R. Udupa, S. Yao, G. Hartzog, and G. Prelich
Phosphorylation of the RNA Polymerase II Carboxy-Terminal Domain by the Bur1 Cyclin-Dependent Kinase
Mol. Cell. Biol., July 1, 2001; 21(13): 4089 - 4096.
[Abstract] [Full Text] [PDF]


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J. Histochem. Cytochem.Home page
A. De Luca, A. Tosolini, P. Russo, A. Severino, A. Baldi, L. De Luca, I. Cavallotti, F. Baldi, A. Giordano, J. R. Testa, et al.
Cyclin T2A Gene Maps on Human Chromosome 2q21
J. Histochem. Cytochem., June 1, 2001; 49(6): 693 - 698.
[Abstract] [Full Text]


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Nucleic Acids ResHome page
S.-H. Chao, A. L. Greenleaf, and D. H. Price
Juglone, an inhibitor of the peptidyl-prolyl isomerase Pin1, also directly blocks transcription
Nucleic Acids Res., February 1, 2001; 29(3): 767 - 773.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
S. M. Foskett, R. Ghose, D. N. Tang, D. E. Lewis, and A. P. Rice
Antiapoptotic Function of Cdk9 (TAK/P-TEFb) in U937 Promonocytic Cells
J. Virol., February 1, 2001; 75(3): 1220 - 1228.
[Abstract] [Full Text]


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J. Cell Sci.Home page
C. Herrmann and M. Mancini
The Cdk9 and cyclin T subunits of TAK/P-TEFb localize to splicing factor-rich nuclear speckle regions
J. Cell Sci., January 4, 2001; 114(8): 1491 - 1503.
[Abstract] [PDF]


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Mol. Cell. Biol.Home page
M. E. Garber, T. P. Mayall, E. M. Suess, J. Meisenhelder, N. E. Thompson, and K. A. Jones
CDK9 Autophosphorylation Regulates High-Affinity Binding of the Human Immunodeficiency Virus Type 1 Tat-P-TEFb Complex to TAR RNA
Mol. Cell. Biol., September 15, 2000; 20(18): 6958 - 6969.
[Abstract] [Full Text]


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Mol. Cell. Biol.Home page
Y. W. Fong and Q. Zhou
Relief of Two Built-In Autoinhibitory Mechanisms in P-TEFb Is Required for Assembly of a Multicomponent Transcription Elongation Complex at the Human Immunodeficiency Virus Type 1 Promoter
Mol. Cell. Biol., August 15, 2000; 20(16): 5897 - 5907.
[Abstract] [Full Text]


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Proc. Natl. Acad. Sci. USAHome page
S. M. Carty, A. C. Goldstrohm, C. Suñé, M. A. Garcia-Blanco, and A. L. Greenleaf
Protein-interaction modules that organize nuclear function: FF domains of CA150 bind the phosphoCTD of RNA polymerase II
PNAS, July 19, 2000; (2000) 160266597.
[Abstract] [Full Text]


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Mol. Cell. Biol.Home page
M. Zhou, M. A. Halanski, M. F. Radonovich, F. Kashanchi, J. Peng, D. H. Price, and J. N. Brady
Tat Modifies the Activity of CDK9 To Phosphorylate Serine 5 of the RNA Polymerase II Carboxyl-Terminal Domain during Human Immunodeficiency Virus Type 1 Transcription
Mol. Cell. Biol., July 15, 2000; 20(14): 5077 - 5086.
[Abstract] [Full Text]


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Nucleic Acids ResHome page
J. W. Steinke, S. J. Kopytek, and D. O. Peterson
Discrete promoter elements affect specific properties of RNA polymerase II transcription complexes
Nucleic Acids Res., July 15, 2000; 28(14): 2726 - 2735.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
M. N. Szentirmay and M. Sawadogo
SURVEY AND SUMMARY: Spatial organization of RNA polymerase II transcription in the nucleus
Nucleic Acids Res., May 15, 2000; 28(10): 2019 - 2025.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
A. L. Lehman and M. E. Dahmus
The Sensitivity of RNA Polymerase II in Elongation Complexes to C-terminal Domain Phosphatase
J. Biol. Chem., May 12, 2000; 275(20): 14923 - 14932.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
D. Ivanov, Y. T. Kwak, J. Guo, and R. B. Gaynor
Domains in the SPT5 Protein That Modulate Its Transcriptional Regulatory Properties
Mol. Cell. Biol., May 1, 2000; 20(9): 2970 - 2983.
[Abstract] [Full Text]


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Mol. Cell. Biol.Home page
D. H. Price
P-TEFb, a Cyclin-Dependent Kinase Controlling Elongation by RNA Polymerase II
Mol. Cell. Biol., April 15, 2000; 20(8): 2629 - 2634.
[Full Text]


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Mol. Cell. Biol.Home page
H. Tang, Y. Liu, L. Madabusi, and D. S. Gilmour
Promoter-Proximal Pausing on the hsp70 Promoter in Drosophila melanogaster Depends on the Upstream Regulator
Mol. Cell. Biol., April 1, 2000; 20(7): 2569 - 2580.
[Abstract] [Full Text]


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Genes Dev.Home page
J. T. Lis, P. Mason, J. Peng, D. H. Price, and J. Werner
P-TEFb kinase recruitment and function at heat shock loci
Genes & Dev., April 1, 2000; 14(7): 792 - 803.
[Abstract] [Full Text]




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