In Vitro Selection of Mutant HDM2 Resistant to Nutlin Inhibition

PLoS ONE

Volumn 8, Issue 4, 2013, Pages

  Wei, Siau Jia ^a,b   Joseph, Thomas ^b   Sim, Adelene Y L ^b   Yurlova, Larisa ^c   Zolghadr, Kourosh ^c   Lane, David ^a   Verma, Chandra ^b,d,e   Ghadessy, Farid ^a  

^a AGENCY FOR SCIENCE   (Singapore)

^b BIOINFORMATICS INSTITUTE   (Singapore)

^c CHROMOTEK GMBH   (Germany)

^d NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

^e NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

NUTLIN 3; PROTEIN MDM2; PROTEIN P53;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; EMBRYO; EX VIVO STUDY; IN VITRO STUDY; MOUSE; MUTATIONAL ANALYSIS; NONHUMAN; PHENOTYPE; PROTEIN DETERMINATION; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; SIMULATION; TRANSACTIVATION; WILD TYPE;

ANIMALS; ANTINEOPLASTIC AGENTS; BINDING SITES; FIBROBLASTS; GENE EXPRESSION; GENE LIBRARY; HUMANS; IMIDAZOLES; MICE; MOLECULAR DOCKING SIMULATION; MUTATION; PIPERAZINES; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84876999513     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0062564     Document Type: Article

References (63)

1. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW, (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51: 6304-6311.
2. Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB, (1992) Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A 89: 7491-7495.
3. Beroud C, Soussi T, (2003) The UMD-p53 database: new mutations and analysis tools. Hum Mutat 21: 176-181.
4. Kan Z, Jaiswal BS, Stinson J, Janakiraman V, Bhatt D, et al. (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466: 869-873.
5. Momand J, Zambetti GP, Olson DC, George D, Levine AJ, (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237-1245.
6. Haupt Y, Maya R, Kazaz A, Oren M, (1997) Mdm2 promotes the rapid degradation of p53. Nature 387: 296-299.
7. Kubbutat MH, Jones SN, Vousden KH, (1997) Regulation of p53 stability by Mdm2. Nature 387: 299-303.
8. Honda R, Tanaka H, Yasuda H, (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420: 25-27.
9. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, et al. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303: 844-848.
10. Bernal F, Tyler AF, Korsmeyer SJ, Walensky LD, Verdine GL, (2007) Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J Am Chem Soc 129: 2456-2457.
11. Liu M, Li C, Pazgier M, Mao Y, Lv Y, et al. (2010) D-peptide inhibitors of the p53-MDM2 interaction for targeted molecular therapy of malignant neoplasms. Proc Natl Acad Sci U S A 107: 14321-14326.
12. Shangary S, Wang S, (2009) Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy. Annu Rev Pharmacol Toxicol 49: 223-241.
13. Brennan RC, Federico S, Bradley C, Zhang J, Flores-Otero J, et al. (2011) Targeting the p53 pathway in retinoblastoma with subconjunctival Nutlin-3a. Cancer Res 71: 4205-4213.
14. Secchiero P, Bosco R, Celeghini C, Zauli G, (2011) Recent advances in the therapeutic perspectives of Nutlin-3. Curr Pharm Des 17: 569-577.
15. Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, et al. (2012) Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol 13: 1133-1140.
16. Aziz MH, Shen H, Maki CG, (2011) Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3. Oncogene 30: 4678-4686.
17. Shen H, Moran DM, Maki CG, (2008) Transient nutlin-3a treatment promotes endoreduplication and the generation of therapy-resistant tetraploid cells. Cancer Res 68: 8260-8268.
18. Tamborini E, Della Torre G, Lavarino C, Azzarelli A, Carpinelli P, et al. (2001) Analysis of the molecular species generated by MDM2 gene amplification in liposarcomas. Int J Cancer 92: 790-796.
19. Schlott T, Reimer S, Jahns A, Ohlenbusch A, Ruschenburg I, et al. (1997) Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours. J Pathol 182: 54-61.
20. Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, et al. (2004) A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 119: 591-602.
21. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B, (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358: 80-83.
22. Zhou M, Gu L, Abshire TC, Homans A, Billett AL, et al. (2000) Incidence and prognostic significance of MDM2 oncoprotein overexpression in relapsed childhood acute lymphoblastic leukemia. Leukemia 14: 61-67.
23. Joseph TL, Madhumalar A, Brown CJ, Lane DP, Verma CS, (2010) Differential binding of p53 and nutlin to MDM2 and MDMX: computational studies. Cell Cycle 9: 1167-1181.
24. Fen CX, Coomber DW, Lane DP, Ghadessy FJ, (2007) Directed evolution of p53 variants with altered DNA-binding specificities by in vitro compartmentalization. J Mol Biol 371: 1238-1248.
25. Zaccolo M, Gherardi E, (1999) The effect of high-frequency random mutagenesis on in vitro protein evolution: a study on TEM-1 beta-lactamase. J Mol Biol 285: 775-783.
26. Montes de Oca Luna R, Wagner DS, Lozano G, (1995) Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378: 203-206.
27. Takahashi T, Carbone D, Nau MM, Hida T, Linnoila I, et al. (1992) Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions. Cancer Res 52: 2340-2343.
28. Zolghadr K, Mortusewicz O, Rothbauer U, Kleinhans R, Goehler H, et al. (2008) A fluorescent two-hybrid assay for direct visualization of protein interactions in living cells. Mol Cell Proteomics 7: 2279-2287.
29. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, et al. (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274: 948-953.
30. Rew Y, Sun D, Gonzalez-Lopez De Turiso F, Bartberger MD, Beck HP, et al. (2012) Structure-based design of novel inhibitors of the MDM2-p53 interaction. J Med Chem 55: 4936-4954.
31. D.A Case, T.A Darden, T.E. Cheatham I, C.L Simmerling, J Wang, et al. (2010) AMBER 11. University of California, San Francisco.
32. Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM, et al. (1995) A second-generation force field for the simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc 117: 5179-5197.
33. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA, (2004) Development and testing of a general AMBER force field. J Comput Chem 25: 1157-1174.
34. Yu GW, Rudiger S, Veprintsev D, Freund S, Fernandez-Fernandez MR, et al. (2006) The central region of HDM2 provides a second binding site for p53. Proc Natl Acad Sci U S A 103: 1227-1232.
35. de Vries SJ, van Dijk M, Bonvin AM, (2010) The HADDOCK web server for data-driven biomolecular docking. Nat Protoc 5: 883-897.
36. Raveh B, London N, Zimmerman L, Schueler-Furman O, (2011) Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors. PLoS One 6: e18934.
37. Noureddine MA, Menendez D, Campbell MR, Bandele OJ, Horvath MM, et al. (2009) Probing the functional impact of sequence variation on p53-DNA interactions using a novel microsphere assay for protein-DNA binding with human cell extracts. PLoS Genet 5: e1000462.
38. Chen J, Marechal V, Levine AJ, (1993) Mapping of the p53 and mdm-2 interaction domains. Mol Cell Biol 13: 4107-4114.
39. Marechal V, Elenbaas B, Piette J, Nicolas JC, Levine AJ, (1994) The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol Cell Biol 14: 7414-7420.
40. Yu GW, Allen MD, Andreeva A, Fersht AR, Bycroft M, (2006) Solution structure of the C4 zinc finger domain of HDM2. Protein Sci 15: 384-389.
41. Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM, (2000) Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 275: 8945-8951.
42. Funston G, Goh W, Wei SJ, Tng QS, Brown C, et al. (2012) Binding of Translationally Controlled Tumour Protein to the N-Terminal Domain of HDM2 Is Inhibited by Nutlin-3. PLoS One 7: e42642.
43. Parant J, Chavez-Reyes A, Little NA, Yan W, Reinke V, et al. (2001) Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53. Nat Genet 29: 92-95.
44. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, et al. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293: 876-880.
45. Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, et al. (2008) The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 105: 2070-2075.
46. McCoy MA, Gesell JJ, Senior MM, Wyss DF, (2003) Flexible lid to the p53-binding domain of human Mdm2: implications for p53 regulation. Proc Natl Acad Sci U S A 100: 1645-1648.
47. Uhrinova S, Uhrin D, Powers H, Watt K, Zheleva D, et al. (2005) Structure of free MDM2 N-terminal domain reveals conformational adjustments that accompany p53-binding. J Mol Biol 350: 587-598.
48. Showalter SA, Bruschweiler-Li L, Johnson E, Zhang F, Bruschweiler R, (2008) Quantitative lid dynamics of MDM2 reveals differential ligand binding modes of the p53-binding cleft. J Am Chem Soc 130: 6472-6478.
49. Worrall EG, Worrall L, Blackburn E, Walkinshaw M, Hupp TR, (2010) The effects of phosphomimetic lid mutation on the thermostability of the N-terminal domain of MDM2. J Mol Biol 398: 414-428.
50. Worrall EG, Wawrzynow B, Worrall L, Walkinshaw M, Ball KL, et al. (2009) Regulation of the E3 ubiquitin ligase activity of MDM2 by an N-terminal pseudo-substrate motif. J Chem Biol 2: 113-129.
51. Ma J, Martin JD, Zhang H, Auger KR, Ho TF, et al. (2006) A second p53 binding site in the central domain of Mdm2 is essential for p53 ubiquitination. Biochemistry 45: 9238-9245.
52. Wawrzynow B, Pettersson S, Zylicz A, Bramham J, Worrall E, et al. (2009) A function for the RING finger domain in the allosteric control of MDM2 conformation and activity. J Biol Chem 284: 11517-11530.
53. Bothner B, Lewis WS, DiGiammarino EL, Weber JD, Bothner SJ, et al. (2001) Defining the molecular basis of Arf and Hdm2 interactions. J Mol Biol 314: 263-277.
54. Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH, (2003) Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 3: 577-587.
55. Lindstrom MS, Jin A, Deisenroth C, White Wolf G, Zhang Y, (2007) Cancer-associated mutations in the MDM2 zinc finger domain disrupt ribosomal protein interaction and attenuate MDM2-induced p53 degradation. Mol Cell Biol 27: 1056-1068.
56. Baek S, Kutchukian PS, Verdine GL, Huber R, Holak TA, et al. (2012) Structure of the stapled p53 peptide bound to Mdm2. J Am Chem Soc 134: 103-106.
57. Brown CJ, Quah ST, Jong J, Goh AM, Chiam PC, et al. (2012) Stapled Peptides with Improved Potency and Specificity That Activate p53. ACS Chem Biol.
58. Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J, (2006) MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem 281: 33030-33035.
59. Garraway LA, Janne PA, (2012) Circumventing cancer drug resistance in the era of personalized medicine. Cancer Discov 2: 214-226.
60. Guo T, Hajdu M, Agaram NP, Shinoda H, Veach D, et al. (2009) Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance. Clin Cancer Res 15: 6862-6870.
61. Azam M, Latek RR, Daley GQ, (2003) Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 112: 831-843.
62. Emery CM, Vijayendran KG, Zipser MC, Sawyer AM, Niu L, et al. (2009) MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A 106: 20411-20416.
63. Tawfik DS, Griffiths AD, (1998) Man-made cell-like compartments for molecular evolution. Nat Biotechnol 16: 652-656.