Small molecule induced reactivation of mutant p53 in cancer cells

Nucleic Acids Research

Volumn 41, Issue 12, 2013, Pages 6034-6044

  Liu, Xiangrui ^a   Wilcken, Rainer ^a   Joerger, Andreas C ^a   Chuckowree, Irina S ^b   Amin, Jahangir ^b   Spencer, John ^b   Fersht, Alan R ^a  

^a MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

^b UNIVERSITY OF SUSSEX   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CASPASE 3; CASPASE 7; NUTLIN 3; PK 7088; PROTEIN BAX; PROTEIN NOXA; PROTEIN P21; PROTEIN P53; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CANCER CELL; CELL CYCLE ARREST; CONCENTRATION RESPONSE; CONTROLLED STUDY; DISSOCIATION CONSTANT; DRUG MECHANISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG STRUCTURE; IN VITRO STUDY; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FOLDING; WILD TYPE; X RAY CRYSTALLOGRAPHY;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-2-ASSOCIATED X PROTEIN; CASPASE 3; CASPASE 7; CELL CYCLE; CELL LINE, TUMOR; GENES, P53; HUMANS; MUTATION; PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-BCL-2; PYRAZOLES; PYRROLES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84880234835     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkt305     Document Type: Article

References (53)

1. Lane, D.P. (1992) Cancer. p53, guardian of the genome. Nature, 358, 15-16.
2. Joerger, A.C. and Fersht, A.R. (2008) Structural biology of the tumor suppressor p53. Annu. Rev. Biochem., 77, 557-582.
3. Vousden, K.H. and Prives, C. (2009) Blinded by the light: the growing complexity of p53. Cell, 137, 413-431.
4. Walerych, D., Napoli, M., Collavin, L. and Del Sal, G. (2012) The rebel angel: mutant p53 as the driving oncogene in breast cancer. Carcinogenesis, 33, 2007-2017.
5. Wattel, E., Preudhomme, C., Hecquet, B., Vanrumbeke, M., Quesnel, B., Dervite, I., Morel, P. and Fenaux, P. (1994) p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood, 84, 3148-3157.
6. Joerger, A.C. and Fersht, A.R. (2007) Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene, 26, 2226-2242.
7. Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S.V., Hainaut, P. and Olivier, M. (2007) Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum. Mutat., 28, 622-629.
8. Joerger, A.C. and Fersht, A.R. (2010) The tumor suppressor p53: from structures to drug discovery. Cold Spring Harb. Perspect. Biol., 2, a000919.
9. Bullock, A.N., Henckel, J., DeDecker, B.S., Johnson, C.M., Nikolova, P.V., Proctor, M.R., Lane, D.P. and Fersht, A.R. (1997) Thermodynamic stability of wild-type and mutant p53 core domain. Proc. Natl Acad. Sci. USA, 94, 14338-14342.
10. Bullock, A.N., Henckel, J. and Fersht, A.R. (2000) Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy. Oncogene, 19, 1245-1256.
11. Joerger, A.C., Ang, H.C. and Fersht, A.R. (2006) Structural basis for understanding oncogenic p53 mutations and designing rescue drugs. Proc. Natl Acad. Sci. USA, 103, 15056-15061.
12. Boeckler, F.M., Joerger, A.C., Jaggi, G., Rutherford, T.J., Veprintsev, D.B. and Fersht, A.R. (2008) Targeted rescue of a destabilized mutant of p53 by an in silico screened drug. Proc. Natl Acad. Sci. USA, 105, 10360-10365.
13. Wilcken, R., Liu, X., Zimmermann, M.O., Rutherford, T.J., Fersht, A.R., Joerger, A.C. and Boeckler, F.M. (2012) Halogen-enriched fragment libraries as leads for drug rescue of mutant p53. J. Am. Chem. Soc., 134, 6810-6818.
14. Brown, C.J., Lain, S., Verma, C.S., Fersht, A.R. and Lane, D.P. (2009) Awakening guardian angels: drugging the p53 pathway. Nat. Rev. Cancer, 9, 862-873.
15. Foster, B.A., Coffey, H.A., Morin, M.J. and Rastinejad, F. (1999) Pharmacological rescue of mutant p53 conformation and function. Science, 286, 2507-2510.
16. Rippin, T.M., Bykov, V.J., Freund, S.M., Selivanova, G., Wiman, K.G. and Fersht, A.R. (2002) Characterization of the p53-rescue drug CP-31398 in vitro and in living cells. Oncogene, 21, 2119-2129.
17. Johnson, W.D., Muzzio, M., Detrisac, C.J., Kapetanovic, I.M., Kopelovich, L. and McCormick, D.L. (2011) Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs. Toxicology, 289, 141-150.
18. Chuckowree, I., Syed, M.A., Getti, G., Patel, A.P., Garner, H., Tizzard, G.J., Coles, S.J. and Spencer, J. (2012) Synthesis of a 1, 3, 5-benzotriazepine-2, 4-dione based library. Tetrahedron Lett., 53, 3607-3611.
19. Spencer, J., Baltus, C.B., Patel, H., Press, N.J., Callear, S.K., Male, L. and Coles, S.J. (2011) Microwave-mediated synthesis of an arylboronate library. ACS Comb. Sci., 13, 24-31.
20. Spencer, J., Baltus, C.B., Press, N.J., Harrington, R.W. and Clegg, W. (2011) Synthesis of a (piperazin-1-ylmethyl)biaryl library via microwave-mediated Suzuki-Miyaura cross-couplings. Tetrahedron Lett., 52, 3963-3968.
21. Spencer, J., Patel, H., Amin, J., Callear, S.K., Coles, S.J., Deadman, J.J., Furman, C., Mansouri, R., Chavatte, P. and Millet, R. (2012) Microwave-mediated synthesis and manipulation of a 2-substituted-5-aminooxazole- 4-carbonitrile library. Tetrahedron Lett., 53, 1656-1659.
22. Spencer, J., Patel, H., Callear, S.K., Coles, S.J. and Deadman, J.J. (2011) Synthesis and solid state study of pyridine-and pyrimidine-based fragment libraries. Tetrahedron Lett., 52, 5905-5909.
23. Spencer, J., Rathnam, R.P., Harvey, A.L., Clements, C.J., Clark, R.L., Barrett, M.P., Wong, P.E., Male, L., Coles, S.J. and Mackay, S.P. (2011) Synthesis and biological evaluation of 1, 4-benzodiazepin-2-ones with antitrypanosomal activity. Bioorg. Med. Chem., 19, 1802-1815.
24. Goddard, T.D. and Kneller, D.G. University of California, San Francisco.
25. Kabsch, W. (2010) Xds. Acta Crystallogr., Sect. D: Biol. Crystallogr., 66, 125-132.
26. Leslie, A.G. (1999) Integration of macromolecular diffraction data. Acta Crystallogr., Sect. D: Biol. Crystallogr., 55, 1696-1702.
27. Adams, P.D., Grosse-Kunstleve, R.W., Hung, L.W., Ioerger, T.R., McCoy, A.J., Moriarty, N.W., Read, R.J., Sacchettini, J.C., Sauter, N.K. and Terwilliger, T.C. (2002) PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr., Sect. D: Biol. Crystallogr., 58, 1948-1954.
28. Emsley, P., Lohkamp, B., Scott, W.G. and Cowtan, K. (2010) Features and development of Coot. Acta Crystallogr., Sect. D: Biol. Crystallogr., 66, 486-501.
29. Liu, X., Shi, S., Lam, F., Pepper, C., Fischer, P.M. and Wang, S. (2012) CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol. Int. J. Cancer, 130, 1216-1226.
30. Gannon, J.V., Greaves, R., Iggo, R. and Lane, D.P. (1990) Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J., 9, 1595-1602.
31. Legros, Y., Meyer, A., Ory, K. and Soussi, T. (1994) Mutations in p53 produce a common conformational effect that can be detected with a panel of monoclonal antibodies directed toward the central part of the p53 protein. Oncogene, 9, 3689-3694.
32. Cook, A. and Milner, J. (1990) Evidence for allosteric variants of wild-type p53, a tumour suppressor protein. Br. J. Cancer, 61, 548-552.
33. Newhouse, B.J., Hansen, J.D., Grina, J., Welch, M., Topalov, G., Littman, N., Callejo, M., Martinson, M., Galbraith, S., Laird, E.R. et al. (2011) Non-oxime pyrazole based inhibitors of B-Raf kinase. Bioorg. Med. Chem. Lett., 21, 3488-3492.
34. Wilcken, R., Wang, G., Boeckler, F.M. and Fersht, A.R. (2012) Kinetic mechanism of p53 oncogenic mutant aggregation and its inhibition. Proc. Natl Acad. Sci. USA, 109, 13584-13589.
35. Wang, G. and Fersht, A.R. (2012) First-order rate-determining aggregation mechanism of p53 and its implications. Proc. Natl Acad. Sci. USA, 109, 13590-13595.
36. Yu, X., Vazquez, A., Levine, A.J. and Carpizo, D.R. (2012) Allele-specific p53 mutant reactivation. Cancer Cell, 21, 614-625.
37. Dearth, L.R., Qian, H., Wang, T., Baroni, T.E., Zeng, J., Chen, S.W., Yi, S.Y. and Brachmann, R.K. (2007) Inactive full-length p53 mutants lacking dominant wild-type p53 inhibition highlight loss of heterozygosity as an important aspect of p53 status in human cancers. Carcinogenesis, 28, 289-298.
38. Di Como, C.J. and Prives, C. (1998) Human tumor-derived p53 proteins exhibit binding site selectivity and temperature sensitivity for transactivation in a yeast-based assay. Oncogene, 16, 2527-2539.
39. Taylor, W.R. and Stark, G.R. (2001) Regulation of the G2/M transition by p53. Oncogene, 20, 1803-1815.
40. Vassilev, L.T., Vu, B.T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C. et al. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 303, 844-848.
41. Kojima, K., Konopleva, M., Samudio, I.J., Shikami, M., Cabreira-Hansen, M., McQueen, T., Ruvolo, V., Tsao, T., Zeng, Z., Vassilev, L.T. et al. (2005) MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood, 106, 3150-3159.
42. Van Maerken, T., Ferdinande, L., Taildeman, J., Lambertz, I., Yigit, N., Vercruysse, L., Rihani, A., Michaelis, M., Cinatl, J. Jr, Cuvelier, C.A. et al. (2009) Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J. Natl Cancer Inst., 101, 1562-1574.
43. Endo, S., Yamato, K., Hirai, S., Moriwaki, T., Fukuda, K., Suzuki, H., Abei, M., Nakagawa, I. and Hyodo, I. (2011) Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells. Cancer Sci., 102, 605-613.
44. Hengartner, M.O. (2000) The biochemistry of apoptosis. Nature, 407, 770-776.
45. Villunger, A., Michalak, E.M., Coultas, L., Mullauer, F., Bock, G., Ausserlechner, M.J., Adams, J.M. and Strasser, A. (2003) p53-and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science, 302, 1036-1038.
46. Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T. and Tanaka, N. (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science, 288, 1053-1058.
47. Lambert, J.M., Gorzov, P., Veprintsev, D.B., Soderqvist, M., Segerback, D., Bergman, J., Fersht, A.R., Hainaut, P., Wiman, K.G. and Bykov, V.J. (2009) PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell, 15, 376-388.
48. Kaar, J.L., Basse, N., Joerger, A.C., Stephens, E., Rutherford, T.J. and Fersht, A.R. (2010) Stabilization of mutant p53 via alkylation of cysteines and effects on DNA binding. Protein Sci., 19, 2267-2278.
49. Speidel, D. (2010) Transcription-independent p53 apoptosis: an alternative route to death. Trends Cell Biol., 20, 14-24.
50. Green, D.R. and Kroemer, G. (2009) Cytoplasmic functions of the tumour suppressor p53. Nature, 458, 1127-1130.
51. Wolter, K.G., Hsu, Y.T., Smith, C.L., Nechushtan, A., Xi, X.G. and Youle, R.J. (1997) Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol., 139, 1281-1292.
52. Chipuk, J.E., Kuwana, T., Bouchier-Hayes, L., Droin, N.M., Newmeyer, D.D., Schuler, M. and Green, D.R. (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science, 303, 1010-1014.
53. Kojima, K., Konopleva, M., McQueen, T., O'Brien, S., Plunkett, W. and Andreeff, M. (2006) Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia. Blood, 108, 993-1000.