Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor

British Journal of Pharmacology

Volumn 171, Issue 1, 2014, Pages 55-68

  Albert, T K ^a   Rigault, C ^a,d   Eickhoff, J ^b   Baumgart, K ^a   Antrecht, C ^a   Klebl, B ^b   Mittler, G ^c   Meisterernst, M ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b Lead Discovery Center GmbH   (Germany)

^c MAX PLANCK INSTITUTE OF IMMUNOBIOLOGY AND EPIGENETICS   (Germany)

^d UNIVERSITÉ DE BOURGOGNE   (France)

Author keywords

CDK9; cyclin dependent kinase; gene expression; RNA polymerase II; transcription

Indexed keywords

5,6 DICHLOROBENZIMIDAZOLE RIBOSIDE; [3 [[6 (2 METHOXYPHENYL)PYRIMIDIN 4 YL]AMINO]PHENYL]METHANESULFONAMIDE; CYCLIN DEPENDENT KINASE 9; CYCLIN DEPENDENT KINASE INHIBITOR; FLAVOPIRIDOL; LDC 000067; MESSENGER RNA; RNA POLYMERASE II; UNCLASSIFIED DRUG;

ANIMAL CELL; APOPTOSIS; ARTICLE; CANCER CELL; CELL PROLIFERATION; CONTROLLED STUDY; DRUG SELECTIVITY; EMBRYO; ENZYME ACTIVITY; ENZYME INHIBITION; FEMALE; GENE EXPRESSION PROFILING; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; IN VITRO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; RNA SYNTHESIS;

CDK9; CYCLIN-DEPENDENT KINASE; GENE EXPRESSION; RNA POLYMERASE II; TRANSCRIPTION;

ADENOSINE TRIPHOSPHATE; ANIMALS; APOPTOSIS; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE 9; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; GENE EXPRESSION REGULATION, NEOPLASTIC; HCT116 CELLS; HEK293 CELLS; HELA CELLS; HUMANS; MCF-7 CELLS; MICE; MICRORNAS; MOLECULAR TARGETED THERAPY; PROTEIN KINASE INHIBITORS; PYRIMIDINES; RNA POLYMERASE II; RNA, MESSENGER; SIGNAL TRANSDUCTION; SULFONAMIDES; TRANSCRIPTION, GENETIC; TRANSFECTION;

EID: 84890290454     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12408     Document Type: Article

References (64)

1. Albert TK, Grote K, Boeing S, Meisterernst M, (2010). Basal core promoters control the equilibrium between negative cofactor 2 and preinitiation complexes in human cells. Genome Biol 11: R33.
2. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR, (2011). Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29: 1039-1045.
3. Bao ZQ, Jacobsen DM, Young MA, (2011). Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis. Structure 19: 675-690.
4. Bartkowiak B, Liu P, Phatnani HP, Fuda NJ, Cooper JJ, Price DH, et al. (2010). CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev 24: 2303-2316.
5. Bird G, Zorio DA, Bentley DL, (2004). RNA polymerase II carboxy-terminal domain phosphorylation is required for cotranscriptional pre-mRNA splicing and 3'-end formation. Mol Cell Biol 24: 8963-8969.
6. Blazek D, Kohoutek J, Bartholomeeusen K, Johansen E, Hulinkova P, Luo Z, et al. (2011). The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev 25: 2158-2172.
7. Boeing S, Rigault C, Heidemann M, Eick D, Meisterernst M, (2010). RNA polymerase II C-terminal heptarepeat domain Ser-7 phosphorylation is established in a mediator-dependent fashion. J Biol Chem 285: 188-196.
8. Bottardi S, Zmiri FA, Bourgoin V, Ross J, Mavoungou L, Milot E, (2011). Ikaros interacts with P-TEFb and cooperates with GATA-1 to enhance transcription elongation. Nucleic Acids Res 39: 3505-3519.
9. Byrd JC, Lin TS, Dalton JT, Wu D, Phelps MA, Fischer B, et al. (2007). Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood 109: 399-404.
10. Caracciolo V, Laurenti G, Romano G, Carnevale V, Cimini AM, Crozier-Fitzgerald C, et al. (2012). Flavopiridol induces phosphorylation of AKT in a human glioblastoma cell line, in contrast to siRNA-mediated silencing of Cdk9: implications for drug design and development. Cell Cycle 11: 1202-1216.
11. Chao SH, Price DH, (2001). Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo. J Biol Chem 276: 31793-31799.
12. Chao SH, Fujinaga K, Marion JE, Taube R, Sausville EA, Senderowicz AM, et al. (2000). Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. J Biol Chem 275: 28345-28348.
13. Chen R, Keating MJ, Gandhi V, Plunkett W, (2005). Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood 106: 2513-2519.
14. Cox ML, Meek DW, (2010). Phosphorylation of serine 392 in p53 is a common and integral event during p53 induction by diverse stimuli. Cell Signal 22: 564-571.
15. Esquela-Kerscher A, Slack FJ, (2006). Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer 6: 259-269.
16. Filipowicz W, Pogacic V, (2002). Biogenesis of small nucleolar ribonucleoproteins. Curr Opin Cell Biol 14: 319-327.
17. Fisher RP, (2005). Secrets of a double agent: CDK7 in cell-cycle control and transcription. J Cell Sci 118: 5171-5180.
18. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, et al. (2004). Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 3: 1427-1438.
19. Fuda NJ, Ardehali MB, Lis JT, (2009). Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature 461: 186-192.
20. Fujinaga K, Irwin D, Huang Y, Taube R, Kurosu T, Peterlin BM, (2004). Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element. Mol Cell Biol 24: 787-795.
21. Garriga J, Grana X, (2004). Cellular control of gene expression by T-type cyclin/CDK9 complexes. Gene 337: 15-23.
22. Garriga J, Xie H, Obradovic Z, Grana X, (2010). Selective control of gene expression by CDK9 in human cells. J Cell Physiol 222: 200-208.
23. Glover-Cutter K, Kim S, Espinosa J, Bentley DL, (2008). RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes. Nat Struct Mol Biol 15: 71-78.
24. Guha M, (2013). Blockbuster dreams for Pfizer's CDK inhibitor. Nat Biotechnol 31: 187.
25. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. (2005). A microRNA polycistron as a potential human oncogene. Nature 435: 828-833.
26. Hou T, Ray S, Brasier AR, (2007). The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression. J Biol Chem 282: 37091-37102.
27. Isel C, Karn J, (1999). Direct evidence that HIV-1 Tat stimulates RNA polymerase II carboxyl-terminal domain hyperphosphorylation during transcriptional elongation. J Mol Biol 290: 929-941.
28. Ivanov D, Kwak YT, Guo J, Gaynor RB, (2000). Domains in the SPT5 protein that modulate its transcriptional regulatory properties. Mol Cell Biol 20: 2970-2983.
29. Jacobsen DM, Bao ZQ, O'brien P, Brooks CL, 3rd, Young MA, (2012). Price to be paid for two-metal catalysis: magnesium ions that accelerate chemistry unavoidably limit product release from a protein kinase. J Am Chem Soc 134: 15357-15370.
30. Kanazawa S, Okamoto T, Peterlin BM, (2000). Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection. Immunity 12: 61-70.
31. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, et al. (2008). A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 26: 127-132.
32. Karp JE, Garrett-Mayer EL, Estey EH, Rudek MA, Smith BD, Greer JM, et al. (2012). Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Haematologica 97: 1736-1742.
33. Konig A, Schwartz GK, Mohammad RM, Al-Katib A, Gabrilove JL, (1997). The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines. Blood 90: 4307-4312.
34. Lam LT, Pickeral OK, Peng AC, Rosenwald A, Hurt EM, Giltnane JM, et al. (2001). Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol 2: RESEARCH0041.
35. Li J, Gilmour DS, (2011). Promoter proximal pausing and the control of gene expression. Curr Opin Genet Dev 21: 231-235.
36. Lis JT, Mason P, Peng J, Price DH, Werner J, (2000). P-TEFb kinase recruitment and function at heat shock loci. Genes Dev 14: 792-803.
37. Liu X, Shi S, Lam F, Pepper C, Fischer PM, Wang S, (2012). CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol. Int J Cancer 130: 1216-1226.
38. Ljungman M, Zhang F, Chen F, Rainbow AJ, McKay BC, (1999). Inhibition of RNA polymerase II as a trigger for the p53 response. Oncogene 18: 583-592.
39. Loyer P, Trembley JH, Katona R, Kidd VJ, Lahti JM, (2005). Role of CDK/cyclin complexes in transcription and RNA splicing. Cell Signal 17: 1033-1051.
40. Ma Y, Cress WD, Haura EB, (2003). Flavopiridol-induced apoptosis is mediated through up-regulation of E2F1 and repression of Mcl-1. Mol Cancer Ther 2: 73-81.
41. Malumbres M, Barbacid M, (2005). Mammalian cyclin-dependent kinases. Trends Biochem Sci 30: 630-641.
42. Malumbres M, Barbacid M, (2009). Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9: 153-166.
43. Marshall NF, Price DH, (1995). Purification of P-TEFb, a transcription factor required for the transition into productive elongation. J Biol Chem 270: 12335-12338.
44. Martinez-Rucobo FW, Cramer P, (2013). Structural basis of transcription elongation. Biochim Biophys Acta 1829: 9-19.
45. Martinez-Rucobo FW, Sainsbury S, Cheung AC, Cramer P, (2011). Architecture of the RNA polymerase-Spt4/5 complex and basis of universal transcription processivity. EMBO J 30: 1302-1310.
46. Misra RN, Xiao HY, Kim KS, Lu S, Han WC, Barbosa SA, et al. (2004). N-(cycloalkylamino)acyl-2-aminothiazole inhibitors of cyclin-dependent kinase 2. N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent. J Med Chem 47: 1719-1728.
47. Nguyen VT, Kiss T, Michels AA, Bensaude O, (2001). 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414: 322-325.
48. O'donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT, (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435: 839-843.
49. Parker BW, Kaur G, Nieves-Neira W, Taimi M, Kohlhagen G, Shimizu T, et al. (1998). Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood 91: 458-465.
50. Peterlin BM, Price DH, (2006). Controlling the elongation phase of transcription with P-TEFb. Mol Cell 23: 297-305.
51. Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, et al. (2010). c-Myc regulates transcriptional pause release. Cell 141: 432-445.
52. Shapiro GI, (2006). Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 24: 1770-1783.
53. Shim EY, Walker AK, Shi Y, Blackwell TK, (2002). CDK-9/cyclin T (P-TEFb) is required in two postinitiation pathways for transcription in the C. elegans embryo. Genes Dev 16: 2135-2146.
54. Te Poele RH, Okorokov AL, Joel SP, (1999). RNA synthesis block by 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) triggers p53-dependent apoptosis in human colon carcinoma cells. Oncogene 18: 5765-5772.
55. Uhlmann T, Boeing S, Lehmbacher M, Meisterernst M, (2007). The VP16 activation domain establishes an active mediator lacking CDK8 in vivo. J Biol Chem 282: 2163-2173.
56. Wada T, Takagi T, Yamaguchi Y, Ferdous A, Imai T, Hirose S, et al. (1998). DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev 12: 343-356.
57. Wang S, Fischer PM, (2008). Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology. Trends Pharmacol Sci 29: 302-313.
58. Wang W, Yao X, Huang Y, Hu X, Liu R, Hou D, et al. (2013). Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb. Transcription 4: 39-51.
59. Wohlbold L, Larochelle S, Liao JC, Livshits G, Singer J, Shokat KM, et al. (2006). The cyclin-dependent kinase (CDK) family member PNQALRE/CCRK supports cell proliferation but has no intrinsic CDK-activating kinase (CAK) activity. Cell Cycle 5: 546-554.
60. Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, et al. (1999). NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 97: 41-51.
61. Yang E, Van Nimwegen E, Zavolan M, Rajewsky N, Schroeder M, Magnasco M, et al. (2003). Decay rates of human mRNAs: correlation with functional characteristics and sequence attributes. Genome Res 13: 1863-1872.
62. Yang Z, Zhu Q, Luo K, Zhou Q, (2001). The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414: 317-322.
63. Zhou Q, Li T, Price DH, (2012). RNA polymerase II elongation control. Annu Rev Biochem 81: 119-143.
64. Zhu Y, Pe'ery T, Peng J, Ramanathan Y, Marshall N, Marshall T, et al. (1997). Transcription elongation factor P-TEFb is required for HIV-1 tat transactivation in vitro. Genes Dev 11: 2622-2632.