Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by modulating pre-mRNA splicing

PLoS ONE

Volumn 10, Issue 1, 2015, Pages

  Araki, Shinsuke ^a   Dairiki, Ryo ^a   Nakayama, Yusuke ^a   Murai, Aiko ^a   Miyashita, Risa ^a   Iwatani, Misa ^a   Nomura, Toshiyuki ^a   Nakanishi, Osamu ^a,b  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b NATIONAL INSTITUTE OF BIOMEDICAL INNOVATION   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 HYDROXY 3 METHYLPROPAN 2 YL) N [6 (1H PYRAZOL 4 YL)IMIDAZO[1,2 A]PYRIDIN 2 YL]BENZAMIDE; 4 [2 METHYL 4 (1H TETRAZOL 5 YL)BUTAN 2 YL] N [6 (TRIFLUOROMETHYL)IMIDAZO[1,2 A]PYRIDIN 2 YL]BENZAMIDE; 6 TERT BUTYL N [6 (1H PYRAZOL 4 YL)IMIDAZO[1,2 A]PYRIDIN 2 YL]NICOTINAMIDE; CDC LIKE KINASE 1; CDC LIKE KINASE 2; CDC LIKE KINASE INHIBITOR; MESSENGER RNA PRECURSOR; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; S6 KINASE; SERINE ARGININE PROTEIN KINASE 1; SERINE ARGININE PROTEIN KINASE 2; SERINE ARGININE PROTEIN KINASE 3; SERINE ARGININE RICH PROTEIN; UNCLASSIFIED DRUG; ARGININE; CLK DUAL-SPECIFICITY KINASES; ISOPROTEIN; MESSENGER RNA; MOLECULAR LIBRARY; NUCLEAR PROTEIN; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; RNA BINDING PROTEIN; RNA PRECURSOR;

ALTERNATIVE RNA SPLICING; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL LINE; CANCER INHIBITION; CELL GROWTH; CELL SURVIVAL; COLORECTAL CANCER; CONTROLLED STUDY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SPECIFICITY; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; NON SMALL CELL LUNG CANCER; PROTEIN DEPLETION; RNA DEGRADATION; RNA SEQUENCE; RNA SPLICING; STOP CODON; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; DRUG EFFECTS; GENETICS; HCT116 CELL LINE; METABOLISM; MOLECULAR LIBRARY; PHARMACOLOGY; PHOSPHORYLATION; TUMOR CELL LINE;

APOPTOSIS; ARGININE; CELL LINE, TUMOR; CELL PROLIFERATION; HCT116 CELLS; HUMANS; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN ISOFORMS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES; RNA PRECURSORS; RNA SPLICING; RNA, MESSENGER; RNA-BINDING PROTEINS; SMALL MOLECULE LIBRARIES;

EID: 84920770954     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0116929     Document Type: Article

References (41)

1. Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, et al. (2003) Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 302: 2141-2144. doi: 10.1126/science.1090100 PMID: 14684825
2. Modrek B, Lee CJ (2003) Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss. Nat Genet 34: 177-180. doi: 10.1038/ng1159 PMID: 12730695
3. Matlin AJ, Clark F, Smith CW (2005) Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol 6: 386-398. doi: 10.1038/nrm1645 PMID: 15956978
4. Wahl MC, Will CL, Luhrmann R (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136: 701-718. doi: 10.1016/j.cell.2009.02.009 PMID: 19239890
5. Tuma RS, Stolk JA, Roth MB (1993) Identification and characterization of a sphere organelle protein. J Cell Biol 122: 767-773. doi: 10.1083/jcb.122.4.767 PMID: 8349728
6. Mayeda A, Zahler AM, Krainer AR, Roth MB (1992) Two members of a conserved family of nuclear phosphoproteins are involved in pre-mRNA splicing. Proc Natl Acad Sci U S A 89: 1301-1304. doi: 10.1073/pnas.89.4.1301 PMID: 1741384
7. Twyffels L, Gueydan C, Kruys V (2011) Shuttling SR proteins: more than splicing factors. FEBS J 278: 3246-3255. doi: 10.1111/j.1742-4658.2011.08274.x PMID: 21794093
8. Long JC, Caceres JF (2009) The SR protein family of splicing factors: master regulators of gene expression. Biochem J 417: 15-27. doi: 10.1042/BJ20081501 PMID: 19061484
9. Grosso AR, Martins S, Carmo-Fonseca M (2008) The emerging role of splicing factors in cancer. EMBO Rep.
10. Srebrow A, Kornblihtt AR (2006) The connection between splicing and cancer. J Cell Sci 119: 2635-2641. doi: 10.1242/jcs.03053 PMID: 16787944
11. Tazi J, Durand S, Jeanteur P (2005) The spliceosome: a novel multi-faceted target for therapy. Trends Biochem Sci 30: 469-478. doi: 10.1016/j.tibs.2005.06.002 PMID: 16009556
12. Anczukow O, Rosenberg AZ, Akerman M, Das S, Zhan L, et al. (2012) The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat Struct Mol Biol 19: 220-228. doi: 10.1038/nsmb.2207 PMID: 22245967
13. Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, et al. (2007) The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 14: 185-193. doi: 10.1038/nsmb1209 PMID: 17310252
14. Hayes GM, Carrigan PE, Miller LJ (2007) Serine-arginine protein kinase 1 overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas. Cancer Res 67: 2072-2080. doi: 10.1158/0008-5472.CAN-06-2969 PMID: 17332336
15. Hayes GM, Carrigan PE, Beck AM, Miller LJ (2006) Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma. Cancer Res 66: 3819-3827. doi: 10.1158/0008-5472. CAN-05-4065 PMID: 16585209
16. Zhou Z, Qiu J, Liu W, Zhou Y, Plocinik RM, et al. (2012) The Akt-SRPK-SR axis constitutes a major pathway in transducing EGF signaling to regulate alternative splicing in the nucleus. Mol Cell 47: 422-433. doi: 10.1016/j.molcel.2012.05.014 PMID: 22727668
17. Cazzola M, Rossi M, Malcovati L (2013) Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood 121: 260-269. doi: 10.1182/blood-2012-09-399725 PMID: 23160465
18. Muraki M, Ohkawara B, Hosoya T, Onogi H, Koizumi J, et al. (2004) Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem 279: 24246-24254. doi: 10.1074/jbc.M314298200 PMID: 15010457
19. Kaida D, Motoyoshi H, Tashiro E, Nojima T, Hagiwara M, et al. (2007) Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol 3: 576-583. doi: 10.1038/ nchembio.2007.18 PMID: 17643111
20. Kotake Y, Sagane K, Owa T, Mimori-Kiyosue Y, Shimizu H, et al. (2007) Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat Chem Biol 3: 570-575. doi: 10.1038/nchembio. 2007.16 PMID: 17643112
21. Webb TR, Joyner AS, Potter PM (2013) The development and application of small molecule modulators of SF3b as therapeutic agents for cancer. Drug Discov Today 18: 43-49. doi: 10.1016/j.drudis.2012. 07.013 PMID: 22885522
22. Neugebauer KM, Roth MB (1997) Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription. Genes Dev 11: 1148-1159. doi: 10.1101/gad.11.9.1148 PMID: 9159396
23. Lai MC, Lin RI, Tarn WY (2003) Differential effects of hyperphosphorylation on splicing factor SRp55. Biochem J 371: 937-945. doi: 10.1042/BJ20021827 PMID: 12549978
24. Zhong XY, Ding JH, Adams JA, Ghosh G, Fu XD (2009) Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones. Genes Dev 23: 482-495. doi: 10.1101/gad.1752109 PMID: 19240134
25. Colwill K, Pawson T, Andrews B, Prasad J, Manley JL, et al. (1996) The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J 15: 265-275. PMID: 8617202
26. Nayler O, Schnorrer F, Stamm S, Ullrich A (1998) The cellular localization of the murine serine/argi-nine-rich protein kinase CLK2 is regulated by serine 141 autophosphorylation. J Biol Chem 273: 34341-34348. doi: 10.1074/jbc.273.51.34341 PMID: 9852100
27. Sinha R, Allemand E, Zhang Z, Karni R, Myers MP, et al. (2010) Arginine methylation controls the subcellular localization and functions of the oncoprotein splicing factor SF2/ASF. Mol Cell Biol 30: 2762-2774. doi: 10.1128/MCB.01270-09 PMID: 20308322
28. Ma XM, Blenis J (2009) Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10: 307-318. doi: 10.1038/nrm2672 PMID: 19339977
29. Busse D, Doughty RS, Ramsey TT, RussellWE, Price JO, et al. (2000) Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27(KIP1) independent ofMAPK activity. J Biol Chem 275: 6987-6995. doi: 10.1074/jbc.275.10.6987 PMID: 10702262
30. Malumbres M, Perez de Castro I (2014) Aurora kinase A inhibitors: promising agents in antitumoral therapy. Expert Opin Ther Targets: 1-17. PMID: 25200357
31. Bose P, Dai Y, Grant S (2014) Histone deacetylase inhibitor (HDACI) mechanisms of action: Emerging insights. Pharmacol Ther 143: 323-336. doi: 10.1016/j.pharmthera.2014.04.004 PMID: 24769080
32. Rios J, Puhalla S (2011) PARP inhibitors in breast cancer: BRCA and beyond. Oncology (Williston Park) 25: 1014-1025. PMID: 22106552
33. Corrionero A, Minana B, Valcarcel J (2011) Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A. Genes Dev 25: 445-459. doi: 10.1101/gad. 2014311 PMID: 21363963
34. Folco EG, Coil KE, Reed R (2011) The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region. Genes Dev 25: 440-444. doi: 10.1101/gad.2009411 PMID: 21363962
35. Amin EM, Oltean S, Hua J, Gammons MV, Hamdollah-Zadeh M, et al. (2011) WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. Cancer Cell 20: 768-780. doi: 10.1016/j.ccr.2011.10.016 PMID: 22172722
36. Karlas A, Machuy N, Shin Y, Pleissner KP, Artarini A, et al. (2010) Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 463: 818-822. doi: 10.1038/ nature08760 PMID: 20081832
37. Wong R, Balachandran A, Mao AY, Dobson W, Gray-Owen S, et al. (2011) Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy. Retrovirology 8: 47. doi: 10.1186/1742-4690-8-47 PMID: 21682887
38. Nishida A, Kataoka N, Takeshima Y, Yagi M, Awano H, et al. (2011) Chemical treatment enhances skipping of a mutated exon in the dystrophin gene. Nat Commun 2: 308. doi: 10.1038/ncomms1306 PMID: 21556062
39. Uchikawa O, Sakai N, Terao Y, Suzuki H, inventors (2010) Takeda Pharmaceutical Company Ltd., assignee. Fused heterocyclic compound. US patent US2010/0029619.
40. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, et al. (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14: R36. doi: 10.1186/gb-2013-14-4-r36 PMID: 23618408
41. Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25. doi: 10.1186/gb-2009-10-3-r25 PMID: 19261174