P-TEFb compositions, methods and screening assays

Details P-TEFb compositions, methods and screening assays P-TEFb compositions, methods and screening assays

2006-03-28

2006-03-28

Steadman, David J. (Department: 1656)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

C435S419000, C435S252300, C435S254110, C435S320100, C435S194000, C536S023200, C536S023500, C536S024310, C536S024330, C530S350000

Reexamination Certificate

active

07018836

ABSTRACT:
Disclosed is the discovery that the transcription elongation factor termed P-TEFb has a central role in transcription elongation control. P-TEFb is herein shown to phosphorylate RNA polymerase II and to control the transition from abortive into productive elongation mode. P-TEFb has also been discovered to interact with the HIV transcriptional transactivating protein, Tat, showing that P-TEFb is the cellular factor necessary for HIV Tat to effect productive viral mRNA elongation. The invention provides genes encoding P-TEFb subunits, including human genes, and related biological components, and also provides assay methods connected with the control of transcription elongation. Particularly useful assays are those concerning the identification of substances that inhibit viral replication at the transcription elongation stage by inhibiting the binding or functional interaction of viral proteins to P-TEFb.

REFERENCES:
patent: 5453362 (1995-09-01), Lamarco et al.
patent: 0 692 488 (1995-05-01), None
patent: WO 95/30026 (1995-11-01), None
patent: WO 95/32307 (1995-11-01), None
patent: WO 96/17084 (1996-06-01), None
patent: WO 96/26292 (1996-08-01), None
Hillier, L. et al., GenBank Database, Accession No. T83219, Mar. 16, 1995.
Hillier, L. et al., GenBank Database, Accession No. T90767, Mar. 22, 1995.
Peng et al. (1998) J Biol Chem 273:13855-13860.
Matsudaira (1990) Methods Enzymol 182:602-613.
Wozney (1990) Methods Enzymol 182:738-751.
Ausubel et al. “Current Protocols in Molecular Biology”, John Wiley and Sons, Inc., New York, 1997.
Branden et al. “Introduction to Protein Structure”, Garland Publishing Inc., New York, 1991.
Witkowski et al. (1999) Biochemistry 38:11643-11650.
Creighton “Protein Structure,” Oxford University Press, New York, 1990.
Watson et al. “Recombinant DNA,” 2nd Ed., W.H. Freeman and Company, New York, 1992.
Akoulitchev, Makela, Weinberg, and Reinberg, “Requirement for TFIIH kinase activity in transcription by RNA polymerase II,”Nature, 377:557-560, Oct. 12, 1995.
Allison, Wong, Fitzpatrick, Moyle, Ingles, “The C-Terminal Domain of the Largest Subunit of RNA Polymerase II ofSaccharomyces cerevisiae, Drosophila melanogaster, and Mammals: A Conserved Structure with an Essential Function,”Mol. Cell. Biol., 8(1):321-329, Jan. 1988.
Baskaran, Dahmus, Wang, “Tyrosine Phosphorylation of Mammalian RNA Polymerase II Carboxyl-Terminal Domain,”Proc. Natl. Acad. Sci. USA,90:11167-11171, Dec. 1993.
Best, Presky, Swerlick, Burns, Chu, “Cloning of a full-length cDNA sequence encoding a cdc2-related protein kinsase from human endothelial cells,”Biochem. Biophys. Res. Comm., 208(2):562-568, Mar. 17, 1995.
Bullrich, MacLachlan, Sang, Druck, Veronese, Allen, Chiorazzi, Koff, Heubner, Croce et al., “Chromosomal mapping of members of the cdc2 family of protein kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk inhibitor, p27Kip1, to regions involved in human cancer,”Cancer Research, 55(6):1199-1205, Mar. 15, 1995.
Cadena and Dahmus, “Messenger RNA Synthesis in Mammalian Cells Is Catalyzed by the Phosphorylated Form of RNA Polymerase II*”,J. Biol. Chem., 262(26):12468-12474, Sep. 15, 1987.
Chodosh, Fire, Samuels, Sharp, “5,6-Dichloro-1-β-D-Ribofuranosylbenzimidazole Inhibits Transcription Elongation by RNA Polymerase II in Vitro,”J. Biol. Chem.,264(4):2250-2257, Feb. 5, 1989.
Cisek and Corden, “Phosphorylation of RNA Polymerase by the Murine Homologue of the Cell-Cycle Control Protein cdc2,”Nature, 339:679-684, Jun. 29, 1989.
Cujec et al., “The HIV Transactivator TAT Binds to the CDK-Activating Kinase and Activates the Phosphorylation of the Carboxyl-Terminal Domain of RNA Polymerase II,”Genes&Development, 11(20):2645-2657, 1997.
Dahmus, “Phosphorylation of the C-terminal domain of RNA polymerase II,”Biochem. Biophys. Acta, 1261:171-182, 1995.
Dahmus, “The Role of Multisite Phosphorylation in the Regulation of RNA Polymerase II Activity,”Progress in Nucleic Acid Research and Molecular Biology, 48:143-179, 1994.
Desai, Loewenstein, Green, “Isolation of a cellular protein that binds to the human immunodeficiency virus Tat protein and can potentiate transactivation of the viral promoter,”Proc. Natl. Acad. Sci. USA, 88:8875-8879, Oct. 1991.
Dubois, Nguyen, Bellier and Bensaude, “Inhibitors of Transcription Such As 5,6-Dichloro-1-β-D-Ribofuranosylbenzimidazole and Isoquinoline Sulfonamide Derivatives (H-8 and H-7*) Promote Dephosphorylation of the Carboxyl-Terminal Domain of RNA Polymerase II Largest Subunit,”The Journal of Biological Chemistry, 269(18):13331-13336, May 6, 1994.
Dvir, Peterson, Knuth, Lu, Dynan, “Ku Autoantigen Is the Regulatory Component of a Template-Associated protein Kinase That Phosphorylates RNA Polymerase II,”Proc. Natl. Acad. Sci. USA, 89:11920-11924, Dec. 1992.
Egyhazi, Ossoinak, Pigon, Holmgren, Lee, Greenleaf, “Phosphorylation Dependence of the Initiation of Productive Transcription of Balbiani Ring 2 Genes In Living Cells,”Chromosoma, 104:422-433, 1996.
Feaver, Gileadi, Li, Kornberg, “CTD kinase associated with yeast RNA polymerase II initiation factor b,”Cell, 67:1223-1230, Dec. 20, 1991.
Flores, Lu, Reinberg, “Factors Involved in Specific Transcription by Mammalian RNA Polymerase II,”J. Biol. Chem., 267(4):2786-2793, Feb. 5, 1992.
Fraser, Sehgal, Darnell, “Multiple Discrete Sites for Premature RNA Chain Termination Late in Adenovirus-2 Infection: Enhancement by 5,6-Dichloro-1-β-D-Ribofuranosylbenzimidazole,”Proc. Natl. Acad. Sci. USA, 76(6):2571-2575, Jun. 1979.
Garcia and Gaynor, “T he human immunodeficiency virus type-1 long terminal repeat and its role in gene expression,” [Review].Progress in Nucleic Acid Research and Molecular Biology, 49:157-196, 1994.
Grana, De Luca, Sang, Fu, Claudio, Rosenblatt, Morgan, Giordano, “PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro”,Proc. Natl. Acad. Sci. USA, 91:3834-3838, Apr. 1994.
Herrmann and Rice, “Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of the large subunit of RNA polymerase II: Candidate for a Tat cofactor,”J. Virol., 69(3):1612-1620, 1995.
Herrmann and Rice, “Specific interaction of the human immunodeficiency virus Tat proteins with a cellular protein kinase,”Virol., 197:601-608, 1993.
Hermann, Gold, Rice, “Viral transactivators specifically target distinct cellular protein kinases that phosphorylate the RNA polymerase II C-terminal domain,”Nucl. Acids Res., 24(3):501-508, 1996.
Jeang, Chun, Lin, Gatignol, Glabe, Fan, “In vitro and in vivo binding of human immunodeficiency virus Type 1 protein and Sp1 transcription factor,”J. Virol., 67(10):6224-6233, 1993.
Jones and Peterlin, “Control of RNA initiation and elongation at the HIV-1 promoter,” [Review].Annual Review of Biochemistry, 63:717-743, 1994.
Kang and Dahmus, “RNA polymerases IIA and IIO have distinct roles during transcription from the TATA-less murine dihydrofolate reductase promoter,”J. Biol. Chem., 268(33):25033-25040, Nov. 25, 1993.
Kephart, Marshall, Price, “Stability ofDrosophilaRNA polymerase II elongation complexes in vitro,”Mol. Cell. Biol., 12(5):2067-2077, May 1992.
Kim and Dahmus, “The Major Late Promoter of Adenovirus-2 Is Accurately Transcribed by RNA Polymerase IIO, IIA, and IIB*,”J. Biol. Chem., 264(6):3169-3176, Feb. 25, 1989.
Koleske and Young, “The RNA Polymerase II Holoenzyme and Its Implications for Gene Regulation,”Trends Biochem. Sci., 20:113-116, Mar. 1995.
Laub, Jakobovits, Aloni, “5,6-Dichloro-1-β-D-Ribofuranosylbenzimidazole Enhances Premature Termination of Late Transcription of Simi

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