Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia

Science Advances

Volumn 2, Issue 10, 2016, Pages

  Picaud, Sarah ^a   Leonards, Katharina ^b   Lambert, Jean Philippe ^c   Dovey, Oliver ^d   Wells, Christopher ^a   Fedorov, Oleg ^a,e   Monteiro, Octovia ^a,e   Fujisawa, Takao ^f   Wang, Chen Yi ^f   Lingard, Hannah ^a   Tallant, Cynthia ^a,e   Nikbin, Nikzad ^g   Guetzoyan, Lucie ^g   Ingham, Richard ^g   Ley, Steven V ^g   Brennan, Paul ^a,e,f   Muller, Susanne ^a,e   Samsonova, Anastasia ^a   Gingras, Anne Claude ^c,h   Schwaller, Juerg ^b   Vassiliou, George ^d,g,i   Knapp, Stefan ^a,e,j   Filippakopoulos, Panagis ^a,f   more..

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

^c MOUNT SINAI HOSPITAL   (Canada)

^d WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f UNIVERSITY OF OXFORD   (United Kingdom)

^g UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^h UNIVERSITY OF TORONTO   (Canada)

ⁱ CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^j GOETHE UNIVERSITY   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; PROTEINS; TRANSCRIPTION;

ANTI-PROLIFERATIVE ACTIVITIES; CONTEXT DEPENDENT; DRUG DEVELOPMENT; MASTER REGULATORS; NANOMOLAR AFFINITY; PROOF OF PRINCIPLES; PROTEIN COMPLEXES; REGULATORY FUNCTIONS;

DISEASES;

ANTINEOPLASTIC AGENT; TRANSCRIPTION FACTOR; TUMOR PROTEIN;

ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DELIVERY SYSTEM; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; HEK293 CELL LINE; HUMAN; K-562 CELL LINE; LEUKEMIA; METABOLISM; PATHOLOGY; SYNTHESIS;

ANTINEOPLASTIC AGENTS; DRUG DELIVERY SYSTEMS; GENE EXPRESSION REGULATION, LEUKEMIC; HEK293 CELLS; HUMANS; K562 CELLS; LEUKEMIA; NEOPLASM PROTEINS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 85008904230     PISSN: None     EISSN: 23752548     Source Type: Journal    
DOI: 10.1126/sciadv.1600760     Document Type: Article

References (64)

1. P. Filippakopoulos, S. Picaud, M. Mangos, T. Keates, J.-P. Lambert, D. Barsyte-Lovejoy, I. Felletar, R. Volkmer, S. Müller, T. Pawson, A.-C. Gingras, C. H. Arrowsmith, S. Knapp, Histone recognition and large-scale structural analysis of the human bromodomain family. Cell 149, 214-231 (2012).
2. P. Filippakopoulos, S. Knapp, Targeting bromodomains: Epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov. 13, 337-356 (2014).
3. L. R. Vidler, N. Brown, S. Knapp, S. Hoelder, Druggability analysis and structural classification of bromodomain acetyl-lysine binding sites. J. Med. Chem. 55, 7346-7359 (2012).
4. A. C. Belkina, G. V. Denis, BET domain co-regulators in obesity, inflammation and cancer. Nat. Rev. Cancer 12, 465-477 (2012).
5. P. Filippakopoulos, J. Qi, S. Picaud, Y. Shen, W. B. Smith, O. Fedorov, E. M. Morse, T. Keates, T. T. Hickman, I. Felletar, M. Philpott, S. Munro, M. R. McKeown, Y. Wang, A. L. Christie, N. West, M. J. Cameron, B. Schwartz, T. D. Heightman, N. La Thangue, C. A. French, O. Wiest, A. L. Kung, S. Knapp, J. E. Bradner, Selective inhibition of BET bromodomains. Nature 468, 1067-1073 (2010).
6. J. Zuber, J. Shi, E. Wang, A. R. Rappaport, H. Herrmann, E. A. Sison, D. Magoon, J. Qi, K. Blatt, M. Wunderlich, M. J. Taylor, C. Johns, A. Chicas, J. C. Mulloy, S. C. Kogan, P. Brown, P. Valent, J. E. Bradner, S. W. Lowe, C. R. Vakoc, RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478, 524-528 (2011).
7. S. Picaud, D. Da Costa, A. Thanasopoulou, P. Filippakopoulos, P. V. Fish, M. Philpott, O. Fedorov, P. Brennan, M. E. Bunnage, D. R. Owen, J. E. Bradner, P. Taniere, B. O'Sullivan, S. Müller, J. Schwaller, T. Stankovic, S. Knapp, PFI-1, a highly selective protein interaction inhibitor, targeting BET bromodomains. Cancer Res. 73, 3336-3346 (2013).
8. D. A. Hay, O. Fedorov, S. Martin, D. C. Singleton, C. Tallant, C. Wells, S. Picaud, M. Philpott, O. P. Monteiro, C. M. Rogers, S. J. Conway, T. P. C. Rooney, A. Tumber, C. Yapp, P. Filippakopoulos, M. E. Bunnage, S. Müller, S. Knapp, C. J. Schofield, P. E. Brennan, Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains. J. Am. Chem. Soc. 136, 9308-9319 (2014).
9. P. Chen, A. Chaikuad, P. Bamborough, M. Bantscheff, C. Bountra, C.-W. Chung, O. Fedorov, P. Grandi, D. Jung, R. Lesniak, M. Lindon, S. Müller, M. Philpott, R. Prinjha, C. Rogers, C. Selenski, C. Tallant, T. Werner, T. M. Willson, S. Knapp, D. H. Drewry, Discovery and characterization of GSK2801, a selective chemical probe for the bromodomains BAZ2A and BAZ2B. J. Med. Chem. 59, 1410-1424 (2016).
10. N. H. Theodoulou, P. Bamborough, A. J. Bannister, I. Becher, R. A. Bit, K. H. Che, C.-w. Chung, A. Dittmann, G. Drewes, D. H. Drewry, L. Gordon, P. Grandi, M. Leveridge, M. Lindon, A.-M. Michon, J. Molnar, S. C. Robson, N. C. O. Tomkinson, T. Kouzarides, R. K. Prinjha, P. G. Humphreys, Discovery of I-BRD9, a selective cell active chemical probe for bromodomain containing protein 9 inhibition. J. Med. Chem. 59, 1425-1439 (2016).
11. P. G. K. Clark, L. C. C. Vieira, C. Tallant, O. Fedorov, D. C. Singleton, C. M. Rogers, O. P. Monteiro, J. M. Bennett, R. Baronio, S. Müller, D. L. Daniels, J. Méndez, S. Knapp, P. E. Brennan, D. J. Dixon, LP99: Discovery and synthesis of the first selective BRD7/9 bromodomain inhibitor. Angew. Chem. Int. Ed. Engl. 54, 6217-6221 (2015).
12. O. Fedorov, J. Castex, C. Tallant, D. R. Owen, S. Martin, M. Aldeghi, O. Monteiro, P. Filippakopoulos, S. Picaud, J. D. Trzupek, B. S. Gerstenberger, C. Bountra, D. Willmann, C. Wells, M. Philpott, C. Rogers, P. C. Biggin, P. E. Brennan, M. E. Bunnage, R. Schüle, T. Günther, S. Knapp, S. Müller, Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance. Sci. Adv. 1, e1500723 (2015).
13. H. Nakano, S. Omura, Chemical biology of natural indolocarbazole products: 30 years since the discovery of staurosporine. J. Antibiot. 62, 17-26 (2009).
14. B. S. Park, A. Z. Abdel-Azeem, M. M. Al-Sanea, K. H. Yoo, J. S. Tae, S. H. Lee, Staurosporine analogues from microbial and synthetic sources and their biological activities. Curr. Med. Chem. 20, 3872-3902 (2013).
15. Q. Xi, Z. Wang, A.-I. Zaromytidou, X. H.-F. Zhang, L.-F. Chow-Tsang, J. X. Liu, H. Kim, A. Barlas, K. Manova-Todorova, V. Kaartinen, L. Studer, W. Mark, D. J. Patel, J. Massagué, A poised chromatin platform for TGF-b access to master regulators. Cell 147, 1511-1524 (2011).
16. L. Zeng, Q. Zhang, G. Gerona-Navarro, N. Moshkina, M.-M. Zhou, Structural basis of sitespecific histone recognition by the bromodomains of human coactivators PCAF and CBP/p300. Structure 16, 643-652 (2008).
17. J. Morinière, S. Rousseaux, U. Steuerwald, M. Soler-López, S. Curtet, A.-L. Vitte, J. Govin, J. Gaucher, K. Sadoul, D. J. Hart, J. Krijgsveld, S. Khochbin, C. W. Müller, C. Petosa, Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature 461, 664-668 (2009).
18. W.-W. Tsai, Z. Wang, T. T. Yiu, K. C. Akdemir, W. Xia, S. Winter, C.-Y. Tsai, X. Shi, D. Schwarzer, W. Plunkett, B. Aronow, O. Gozani, W. Fischle, M.-C. Hung, D. J. Patel, M. C. Barton, TRIM24 links a non-canonical histone signature to breast cancer. Nature 468, 927-932 (2010).
19. A. J. Ruthenburg, H. Li, T. A. Milne, S. Dewell, R. K. McGinty, M. Yuen, B. Ueberheide, Y. Dou, T. W. Muir, D. J. Patel, C. D. Allis, Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions. Cell 145, 692-706 (2011).
20. 4 recognition by the human BRD2 bromodomain. J. Biol. Chem. 285, 7610-7618 (2010).
21. O. Fedorov, H. Lingard, C. Wells, O. P. Monteiro, S. Picaud, T. Keates, C. Yapp, M. Philpott, S. J. Martin, I. Felletar, B. D. Marsden, P. Filippakopoulos, S. Müller, S. Knapp, P. E. Brennan, [1, 2, 4]Triazolo[4, 3-A]phthalazines: Inhibitors of diverse bromodomains. J. Med. Chem. 57, 462-476 (2014).
22. C. Kadoch, D. C. Hargreaves, C. Hodges, L. Elias, L. Ho, J. Ranish, G. R. Crabtree, Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat. Genet. 45, 592-601 (2013).
23. W. F. Marzluff, E. J. Wagner, R. J. Duronio, Metabolism and regulation of canonical histone mRNAs: Life without a poly(A) tail. Nat. Rev. Genet. 9, 843-854 (2008).
24. C.-Y. Wang, P. Filippakopoulos, Beating the odds: BETs in disease. Trends Biochem. Sci. 40, 468-479 (2015).
25. C. Y. Fong, O. Gilan, E. Y. N. Lam, A. F. Rubin, S. Ftouni, D. Tyler, K. Stanley, D. Sinha, P. Yeh, J. Morison, G. Giotopoulos, D. Lugo, P. Jeffrey, S. C.-W. Lee, C. Carpenter, R. Gregory, R. G. Ramsay, S. W. Lane, O. Abdel-Wahab, T. Kouzarides, R. W. Johnstone, S.-J. Dawson, B. J. P. Huntly, R. K. Prinjha, A. T. Papenfuss, M. A. Dawson, BET inhibitor resistance emerges from leukaemia stem cells. Nature 525, 538-542 (2015).
26. P. Rathert, M. Roth, T. Neumann, F. Muerdter, J.-S. Roe, M. Muhar, S. Deswal, S. Cerny-Reiterer, B. Peter, J. Jude, T. Hoffmann, L. M. Boryn, E. Axelsson, N. Schweifer, U. Tontsch-Grunt, L. E. Dow, D. Gianni, M. Pearson, P. Valent, A. Stark, N. Kraut, C. R. Vakoc, J. Zuber, Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Nature 525, 543-547 (2015).
27. A. Puissant, S. M. Frumm, G. Alexe, C. F. Bassil, J. Qi, Y. H. Chanthery, E. A. Nekritz, R. Zeid, W. C. Gustfson, P. Greninger, M. J. Garnett, U. McDermott, C. H. Benes, A. L. Kung, W. A. Weiss, J. E. Bradner, K. Stegmaier, Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 3, 308-323 (2013).
28. S. Picaud, O. Fedorov, A. Thanasopoulou, K. Leonards, K. Jones, J. Meier, H. Olzscha, O. Monteiro, S. Martin, M. Philpott, A. Tumber, P. Filippakopoulos, C. Yapp, C. Wells, K. H. Che, A. Bannister, S. Robson, U. Kumar, N. Parr, K. Lee, D. Lugo, P. Jeffrey, S. Taylor, M. L. Vecellio, C. Bountra, P. E. Brennan, A. O'Mahony, S. Velichko, S. Müller, D. Hay, D. L. Daniels, M. Urh, N. B. La Thangue, T. Kouzarides, R. Prinjha, J. Schwaller, S. Knapp, Generation of a selective small molecule inhibitor of the CBP/p300 bromodomain for leukemia therapy. Cancer Res. 75, 5106-5119 (2015).
29. J. Shi, E. Wang, J. P.Milazzo, Z. Wang, J. B. Kinney, C. R. Vakoc, Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains. Nat. Biotechnol. 33, 661-667 (2015).
30. D. Matulis, J. K. Kranz, F. R. Salemme, M. J. Todd, Thermodynamic stability of carbonic anhydrase: Measurements of binding affinity and stoichiometry using Thermo Fluor. Biochemistry 44, 5258-5266 (2005).
31. T. Wiseman, S. Williston, J. F. Brandts, L.-N. Lin, Rapid measurement of binding constants and heats of binding using a new titration calorimeter. Anal. Biochem. 179, 131-137 (1989).
32. W. Kabsch, Evaluation of single-crystal X-ray diffraction data from a position-sensitive detector. J. Appl. Crystallogr. 21, 916-924 (1988).
33. W. Kabsch, Automatic indexing of rotation diffraction patterns. J Appl. Crystallogr. 21, 67-72 (1988).
34. P. Evans, SCALA-Scale Together Multiple Observations of Reflections (MRC Laboratory of Molecular Biology, 2007).
35. A. J. McCoy, R. W. Grosse-Kunstleve, L. C. Storoni, R. J. Read, Likelihood-enhanced fast translation functions. Acta Crystallogr. Sect. D Biol. Crystallogr. 61, 458-464 (2005).
36. A. Perrakis, R. Morris, V. S. Lamzin, Automated protein model building combined with iterative structure refinement. Nat. Struct. Biol. 6, 458-463 (1999).
37. P. Emsley, K. Cowtan, Coot: Model-building tools for molecular graphics. Acta Crystallogr. Sect. D Biol. Crystallogr. 60, 2126-2132 (2004).
38. G. N. Murshudov, A. A. Vagin, E. J. Dodson, Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. Sect. D Biol. Crystallogr. 53, 240-255 (1997).
39. J. Painter, E. A. Merritt, Optimal description of a protein structure in terms of multiple groups undergoing TLS motion. Acta Crystallogr. Sect. D Biol. Crystallogr. D 62, 439-450 (2006).
40. D. Barsyte-Lovejoy, F. Li, M. J. Oudhoff, J. H. Tatlock, A. Dong, H. Zeng, H. Wu, S. A. Freeman, M. Schapira, G. A. Senisterra, E. Kuznetsova, R. Marcellus, A. Allali-Hassani, S. Kennedy, J.-P. Lambert, A. L. Couzens, A. Aman, A.-C. Gingras, R. Al-Awar, P. V. Fish, B. S. Gerstenberger, L. Roberts, C. L. Benn, R. L. Grimley, M. J. S. Braam, F. M. V. Rossi, M. Sudol, P. J. Brown, M. E. Bunnage, D. R. Owen, C. Zaph, M. Vedadi, C. H. Arrowsmith, (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc. Natl. Acad. Sci. U.S.A. 111, 12853-12858 (2014).
41. G. Liu, J. Zhang, B. Larsen, C. Stark, A. Breitkreutz, Z.-Y. Lin, B.-J. Breitkreutz, Y. Ding, K. Colwill, A. Pasculescu, T. Pawson, J. L. Wrana, A. I. Nesvizhskii, B. Raught, M. Tyers, A.-C. Gingras, ProHits: Integrated software for mass spectrometry-based interaction proteomics. Nat. Biotechnol. 28, 1015-1017 (2010).
42. E. W. Deutsch, L. Mendoza, D. Shteynberg, T. Farrah, H. Lam, N. Tasman, Z. Sun, E. Nilsson, B. Pratt, B. Prazen, J. K. Eng, D. B. Martin, A. I. Nesvizhskii, R. Aebersold, A guided tour of the Trans-Proteomic Pipeline. Proteomics 10, 1150-1159 (2010).
43. D. Shteynberg, E. W. Deutsch, H. Lam, J. K. Eng, Z. Sun, N. Tasman, L. Mendoza, R. L. Moritz, R. Aebersold, A. I. Nesvizhskii, iProphet: Multi-level integrative analysis of shotgun proteomic data improves peptide and protein identification rates and error estimates. Mol. Cell. Proteomics 10, M111., 007690 (2011).
44. B. B. Lozzio, C. B. Lozzio, Properties and usefulness of the original K-562 human myelogenous leukemia cell line. Leuk. Res. 3, 363-370 (1979).
45. H. Asou, S. Tashiro, K. Hamamoto, A. Otsuji, K. Kita, N. Kamada, Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation. Blood 77, 2031-2036 (1991).
46. B. Lange, M. Valtieri, D. Santoli, D. Caracciolo, F. Mavilio, I. Gemperlein, C. Griffin, B. Emanuel, J. Finan, P. Nowell, Growth factor requirements of childhood acute leukemia: Establishment of GM-CSF-dependent cell lines. Blood 70, 192-199 (1987).
47. H. Quentmeier, M. P. Martelli, W. G. Dirks, N. Bolli, A. Liso, R. A. F. MacLeod, I. Nicoletti, R. Mannucci, A. Pucciarini, B. Bigerna, M. F. Martelli, C. Mecucci, H. G. Drexler, B. Falini, Acute non lymphocytic leukemia: Cell line OCI/AML3 bears exon-12 NPM gene mutation- A and cytoplasmic expression of nucleophosmin. Leukemia 19, 1760-1767 (2005).
48. R. H. Shoemaker, The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer 6, 813-823 (2006).
49. T.-C. Chou, P. Talalay, Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22, 27-55 (1984).
50. M. Philpott, C. M. Rogers, C. Yapp, C. Wells, J.-P. Lambert, C. Strain-Damerell, N. A. Burgess-Brown, A.-C. Gingras, S. Knapp, S. Müller, Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching. Epigenetics Chromatin 7, 14 (2014).
51. R. D. Phair, S. A. Gorski, T. Misteli, Measurement of dynamic protein binding to chromatin in vivo, using photobleaching microscopy. Methods Enzymol. 375, 393-414 (2004).
52. R. Ihaka, R. Gentleman, R: A language for data analysis and graphics. J. Comput. Graph. Stat. 5, 299-314 (1996).
53. R. C. Gentleman, V. J. Carey, D. M. Bates, B. Bolstad, M. Dettling, S. Dudoit, B. Ellis, L. Gautier, Y. Ge, J. Gentry, K. Hornik, T. Hothorn, W. Huber, S. Iacus, R. Irizarry, F. Leisch, C. Li, M. Maechler, A. J. Rossini, G. Sawitzki, C. Smith, G. Smyth, L. Tierney, J. Y. H. Yang, J. Zhang, Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol. 5, R80 (2004).
54. P. Du, W. A. Kibbe, S. M. Lin, lumi: A pipeline for processing Illumina microarray. Bioinformatics 24, 1547-1548 (2008).
55. A. Kauffmann, R. Gentleman, W. Huber, Array Quality Metrics-A Bioconductor package for quality assessment of microarray data. Bioinformatics 25, 415-416 (2009).
56. S. M. Lin, P. Du, W. Huber, W. A. Kibbe, Model-based variance-stabilizing transformation for Illumina microarray data. Nucleic Acids Res. 36, e11 (2008).
57. M. E. Ritchie, B. Phipson, D. Wu, Y. Hu, C. W. Law, W. Shi, G. K. Smyth, limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
58. Y. Benjamini, Y. Hochberg, Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289-300 (1995).
59. A. Alexa, J. Rahnenfuhrer, T. Lengauer, Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. Bioinformatics 22, 1600-1607 (2006).
60. J. A. Miller, C. Cai, P. Langfelder, D. H. Geschwind, S. M. Kurian, D. R. Salomon, S. Horvath, Strategies for aggregating gene expression data: The collapseRows R function. BMC Bioinformatics 12, 322 (2011).
61. A. Subramanian, P. Tamayo, V. K. Mootha, S. Mukherjee, B. L. Ebert, M. A. Gillette, A. Paulovich, S. L. Pomeroy, T. R. Golub, E. S. Lander, J. P. Mesirov, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U.S.A. 102, 15545-15550 (2005).
62. L. Väremo, J. Nielsen, I. Nookaew, Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods. Nucleic Acids Res. 41, 4378-4391 (2013).
63. B. Efron, R. Tibshirani, On testing the significance of sets of genes. Ann. Appl. Stat. 1, 107-129 (2007).
64. K. J. Livak, T. D. Schmittgen, Analysis of relative gene expression data using real-Time quantitative PCR and the 2-DDC T method. Methods 25, 402-408 (2001).