The p53 tetramer shows an induced-fit interaction of the C-terminal domain with the DNA-binding domain

Oncogene

Volumn 35, Issue 25, 2016, Pages 3272-3281

  D'Abramo, M ^a   Besker N ^b   Desideri, A ^c   Levine, A J ^d,e   Melino, G ^c,f   Chillemi, G ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b CINECA   (Italy)

^c UNIVERSITY OF ROME TOR VERGATA   (Italy)

^d INSTITUTE FOR ADVANCED STUDY   (United States)

^e RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^f UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENINE; DNA; PROTEIN P53; TETRAMER; THYMINE; PROTEIN BINDING;

ARTICLE; BINDING SITE; CARBOXY TERMINAL SEQUENCE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DNA BINDING; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; STATIC ELECTRICITY; CHEMISTRY; CONFORMATION; GENETICS; HUMAN; KINETICS; METABOLISM; MOLECULAR MODEL; MUTATION; PROTEIN MULTIMERIZATION; PROTEIN TERTIARY STRUCTURE; X RAY CRYSTALLOGRAPHY;

BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DNA; HUMANS; KINETICS; MODELS, MOLECULAR; MUTATION; NUCLEIC ACID CONFORMATION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STABILITY; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; STATIC ELECTRICITY; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84975717995     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2015.388     Document Type: Article

References (121)

1. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 2007; 28: 622-629.
2. Leroy B, Fournier JL, Ishioka C, Monti P, Inga A, Fronza G et al. The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis. Nucleic Acids Res 2013; 41: D962-D969.
3. Yoshida K, Miki Y. The cell death machinery governed by the p53 tumor suppressor in response to DNA damage. Cancer Sci 2010; 101: 831-835.
4. Chari NS, Pinaire NL, Thorpe L, Medeiros LJ, Routbort MJ, McDonnell TJ. The p53 tumor suppressor network in cancer and the therapeutic modulation of cell death. Apoptosis 2009; 14: 336-347.
5. Giono LE, Manfredi JJ. The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cell Physiol 2006; 209: 13-20.
6. Feng H, Jenkins LMM, Durell SR, Hayashi R, Mazur SJ, Cherry S et al. Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation. Structure 2009; 17: 202-210.
7. Rowell JP, Simpson KL, Stott K, Watson M, Thomas JO. HMGB1-facilitated p53 DNA binding occurs via HMG-Box/p53 transactivation domain interaction, regulated by the acidic tail. Structure 2012; 20: 2014-2024.
8. Bochkareva E, Kaustov L, Ayed A, Yi G-S, Lu Y, Pineda-Lucena A et al. Singlestranded DNA mimicry in the p53 transactivation domain interaction with replication protein A. Proc Natl Acad Sci USA 2005; 102: 15412-15417.
9. Cho Y, Gorina S, Jeffrey PD, Pavletich NP. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 1994; 265: 346-355.
10. Jeffrey PD, Gorina S, Pavletich NP. Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms. Science 1995; 267: 1498-1502.
11. Cañadillas JMP, Tidow H, Freund SMV, Rutherford TJ, Ang HC, Fersht AR. Solution structure of p53 core domain: structural basis for its instability. Proc Natl Acad Sci USA 2006; 103: 2109-2114.
12. Tidow H, Melero R, Mylonas E, Freund SMV, Grossmann JG, Carazo JM et al. Quaternary structures of tumor suppressor p53 and a specific p53 DNA complex. Proc Natl Acad Sci USA 2007; 104: 12324-12329.
13. Chillemi G, Davidovich P, D'Abramo M, Mametnabiev T, Garabadzhiu AV, Desideri A et al. Molecular dynamics of the full-length p53 monomer. Cell Cycle 2013; 12: 3098-3108.
14. Lubin DJ, Butler JS, Loh SN. Folding of tetrameric p53: oligomerization and tumorigenic mutations induce misfolding and loss of function. J Mol Biol 2010; 395: 705-716.
15. Wassman CD, Baronio R, Demir Ö, Wallentine BD, Chen C-K, Hall LV et al. Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53. Nat Commun 2013; 4: 1407.
16. Demir Ö, Baronio R, Salehi F, Wassman CD, Hall L, Hatfield GW et al. Ensemblebased computational approach discriminates functional activity of p53 cancer and rescue mutants. PLoS Comput Biol 2011; 7: e1002238.
17. Lu Q, Tan Y-H, Luo R. Molecular dynamics simulations of p53 DNAbinding domain. J Phys Chem B 2007; 111: 11538-11545.
18. McCammon JA, Harvey SC. Dynamics of Proteins and Nucleic Acids. Cambridge University Press: Cambridge, UK, 1988, pp 289-302.
19. Van Aalten DMF, de Groot BL, Findlay JBC, Berendsen HJC, Amadei A. A comparison of techniques for calculating protein essential dynamics. J Comput Chem 1997; 18: 169-181.
20. Amadei A, Linssen ABM, Berendsen HJC. Essential dynamics of proteins. Proteins Struct Funct Genet 1993; 17: 412-425.
21. Kern D, Zuiderweg ERP. The role of dynamics in allosteric regulation. Curr Opin Struct Biol 2003; 13: 748-757.
22. Henzler-Wildman K, Kern D. Dynamic personalities of proteins. Nature 2007; 450: 964-972.
23. Lange OF, Grubmüller H. Full correlation analysis of conformational protein dynamics. Proteins Struct Funct Genet 2008; 70: 1294-1312.
24. Melero R, Rajagopalan S, Lázaro M, Joerger AC, Brandt T, Veprintsev DB et al. Electron microscopy studies on the quaternary structure of p53 reveal different binding modes for p53 tetramers in complex with DNA. Proc Natl Acad Sci USA 2011; 108: 557-562.
25. Chen Y, Dey R, Chen L. Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer. Structure 2010; 18: 246-256.
26. Petty TJ, Emamzadah S, Costantino L, Petkova I, Stavridi ES, Saven JG et al. An induced fit mechanism regulates p53 DNA binding kinetics to confer sequence specificity. EMBO J 2011; 30: 2167-2176.
27. Pan Y, Nussinov R. Lysine120 interactions with p53 response elements can allosterically direct p53 organization. PLoS Comput Biol 2010; 6: 1-13.
28. Lavery R, Moakher M, Maddocks JH, Petkeviciute D, Zakrzewska K. Conformational analysis of nucleic acids revisited: Curves+. Nucleic Acids Res 2009; 37: 5917-5929.
29. Lu XJ, Olson WK. 3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. Nucleic Acids Res 2003; 31: 5108-5121.
30. Laptenko O, Shiff I, Freed-Pastor W, Zupnick A, Mattia M, Freulich E et al. The p53 C terminus controls site-specific DNA binding and promotes structural changes within the central DNA binding domain. Mol Cell 2015; 57: 1034-1046.
31. Spolar RS, Record MT. Coupling of local folding to site-specific binding of proteins to DNA. Science 1994; 263: 777-784.
32. Jiang P, Du W, Mancuso A, Wellen KE, Yang X. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 2013; 493: 689-693.
33. Venkatanarayan A, Raulji P, Norton W, Chakravarti D, Coarfa C, Su X et al. IAPPdriven metabolic reprogramming induces regression of p53-deficient tumours in vivo. Nature 2014; 517: 626-630.
34. Méniel V, Megges M, Young MA, Cole A, Sansom OJ, Clarke AR. Apc and p53 interaction in DNA damage and genomic instability in hepatocytes. Oncogene 2014; 34: 4118-4129.
35. Van Nostrand JL, Brady Ca, Jung H, Fuentes DR, Kozak MM, Johnson TM et al. Inappropriate p53 activation during development induces features of CHARGE syndrome. Nature 2014; 514: 228-232.
36. Shetzer Y, Kagan S, Koifman G, Sarig R, Kogan-Sakin I, Charni M et al. The onset of p53 loss of heterozygosity is differentially induced in various stem cell types and may involve the loss of either allele. Cell Death Differ 2014; 21: 1419-1431.
37. Nair BC, Krishnan SR, Sareddy GR, Mann M, Xu B, Natarajan M et al. Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response. Cell Death Differ 2014; 21: 1409-1418.
38. Zhu L, Lu Z, Zhao H. Antitumor mechanisms when pRb and p53 are genetically inactivated. Oncogene 2014; 34: 4547-4557.
39. Merlo P, Frost B, Peng S, Yang YJ, Park PJ, Feany M. p53 prevents neurodegeneration by regulating synaptic genes. Proc Natl Acad Sci USA 2014; 111: 18055-18060.
40. Dudgeon C, Chan C, Kang W, Sun Y, Emerson R, Robins H et al. The evolution of thymic lymphomas in p53 knockout mice. Genes Dev 2014; 28: 2613-2620.
41. Tan EH, Morton JP, Timpson P, Tucci P, Melino G, Flores ER et al. Functions of TAp63 and p53 in restraining the development of metastatic cancer. Oncogene 2014; 33: 3325-3333.
42. Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y et al. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 2012; 149: 1269-1283.
43. Antonov AV, Krestyaninova M, Knight RA, Rodchenkov I, Melino G, Barlev NA. PPISURV: a novel bioinformatics tool for uncovering the hidden role of specific genes in cancer survival outcome. Oncogene 2014; 33: 1621-1628.
44. Kim J, Nakasaki M, Todorova D, Lake B, Yuan C-Y, Jamora C et al. P53 induces skin aging by depleting Blimp1(+) sebaceous gland cells. Cell Death Dis 2014; 5: e1141.
45. Fatt MP, Cancino GI, Miller FD, Kaplan DR. P63 and P73 coordinate P53 function to determine the balance between survival, cell death, and senescence in adult neural precursor cells. Cell Death Differ 2014; 21: 1546-1559.
46. Rufini A, Tucci P, Celardo I, Melino G. Senescence and aging: the critical roles of p53. Oncogene 2013; 32: 5129-5143.
47. Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. The p53 family: guardians of maternal reproduction. Nat Rev Mol Cell Biol 2011; 12: 259-265.
48. Müller M, Schleithoff ES, Stremmel W, Melino G, Krammer PH, Schilling T. One, two, three-p53, p63, p73 and chemosensitivity. Drug Resist Updat 2006; 9: 288-306.
49. Tomasini R, Mak TW, Melino G. The impact of p53 and p73 on aneuploidy and cancer. Trends Cell Biol 2008; 18: 244-252.
50. Tschaharganeh DF, Xue W, Calvisi DF, Evert M, Michurina TV, Dow LE et al. P53-dependent nestin regulation links tumor suppression to cellular plasticity in liver cancer. Cell 2014; 158: 579-592.
51. Weissmueller S, Manchado E, Saborowski M, Morris JP, Wagenblast E, Davis CA et al. Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor β signaling. Cell 2014; 157: 382-394.
52. Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, Bolden JE et al. Noncell-autonomous tumor suppression by p53. Cell 2013; 153: 449-460.
53. Buckley NE, D'Costa Z, Kaminska M, Mullan PB. S100A2 is a BRCA1/p63 coregulated tumour suppressor gene with roles in the regulation of mutant p53 stability. Cell Death Dis 2014; 5: e1070.
54. Xu J, Wang J, Hu Y, Qian J, Xu B, Chen H et al. Unequal prognostic potentials of p53 gain-of-function mutations in human cancers associate with drugmetabolizing activity. Cell Death Dis 2014; 5: e1108.
55. Foijer F, Xie SZ, Simon JE, Bakker PL, Conte N, Davis SH et al. Chromosome instability induced by Mps1 and p53 mutation generates aggressive lymphomas exhibiting aneuploidy-induced stress. Proc Natl Acad Sci USA 2014; 111: 13427-13432.
56. Mello SS, Attardi LD. Not all p53 gain-of-function mutants are created equal. Cell Death Differ 2013; 20: 855-857.
57. Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. P53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 2012; 149: 1536-1548.
58. Maddocks ODK, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E et al. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 2013; 493: 542-546.
59. Amelio I, Markert EK, Rufini A, Antonov AV, Sayan BS, Tucci P et al. P73 regulates serine biosynthesis in cancer. Oncogene 2013; 33: 5039-5046.
60. Evstafieva AG, Garaeva AA, Khutornenko AA, Klepikova AV, Logacheva MD, Penin AA et al. A sustained deficiency of mitochondrial respiratory complex III induces an apoptotic cell death through the p53-mediated inhibition of pro-survival activities of the activating transcription factor 4. Cell Death Dis 2014; 5: e1511.
61. Peuget S, Bonacci T, Soubeyran P, Iovanna J, Dusetti NJ. Oxidative stress-induced p53 activity is enhanced by a redox-sensitive TP53INP1 SUMOylation. Cell Death Differ 2014; 21: 1107-1118.
62. Shi Y, Nikulenkov F, Zawacka-Pankau J, Li H, Gabdoulline R, Xu J et al. ROSdependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis. Cell Death Differ 2014; 21: 612-623.
63. Rufini A, Niklison-Chirou MV, Inoue S, Tomasini R, Harris IS, Marino A et al. TAp73 depletion accelerates aging through metabolic dysregulation. Genes Dev 2012; 26: 2009-2014.
64. Drosten M, Sum EYM, Lechuga CG, Simón-Carrasco L, Jacob HKC, García-Medina R et al. Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway. Proc Natl Acad Sci USA 2014; 111: 15155-15160.
65. Zhang H-H, Li S-Z, Zhang Z-Y, Hu X-M, Hou P-N, Gao L et al. Nemo-like kinase is criticalor p53 stabilization and function in response to DNA damage. Cell Death Differ 2014; 21: 1656-1663.
66. Tang Z, Chen W-Y, Shimada M, Nguyen UTT, Kim J, Sun X-J et al. SET1 and p300 act synergistically, through coupled histone modifications, in transcriptional activation by p53. Cell 2013; 154: 297-310.
67. Dashzeveg N, Taira N, Lu Z-G, Kimura J, Yoshida K. Palmdelphin, a novel target of p53 with Ser46 phosphorylation, controls cell death in response to DNA damage. Cell Death Dis 2014; 5: e1221.
68. Li D, Yallowitz A, Ozog L, Marchenko N. A gain-of-function mutant p53-HSF1 feed forward circuit governs adaptation of cancer cells to proteotoxic stress. Cell Death Dis 2014; 5: e1194.
69. Manzl C, Fava LL, Krumschnabel G, Peintner L, Tanzer MC, Soratroi C et al. Death of p53-defective cells triggered by forced mitotic entry in the presence of DNA damage is not uniquely dependent on caspase-2 or the PIDDosome. Cell Death Dis 2013; 4: e942.
70. Phesse TJ, Myant KB, Cole AM, Ridgway RA, Pearson H, Muncan V et al. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo. Cell Death Differ 2014; 21: 956-966.
71. Gorrini C. Discovery of a p53 variant that controls metastasis. Proc Natl Acad Sci USA 2014; 111: 11576-11577.
72. Senturk S, Yao Z, Camiolo M, Stiles B, Rathod T, Walsh AM et al. P53 Ψ is a transcriptionally inactive P53 isoform able to reprogram cells toward a metastatic-like state. Proc Natl Acad Sci USA 2014; 111: E3287-E3296.
73. Solomon H, Sharon M, Rotter V. Modulation of alternative splicing contributes to cancer development: focusing on p53 isoforms, p53β and p53γ. Cell Death Differ 2014; 21: 1347-1349.
74. Marcel V, Fernandes K, Terrier O, Lane DP, Bourdon J-C. Modulation of p53β and p53γ expression by regulating the alternative splicing of TP53 gene modifies cellular response. Cell Death Differ 2014; 21: 1377-1387.
75. Hoffman Y, Bublik DR, Pilpel Y, Oren M. miR-661 downregulates both Mdm2 and Mdm4 to activate p53. Cell Death Differ 2014; 21: 302-309.
76. Balatti V, Rizzotto L, Miller C, Palamarchuk A, Fadda P, Pandolfo R et al. TCL1 targeting miR-3676 is codeleted with tumor protein p53 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2015; 112: 2169-2174.
77. Fiori ME, Barbini C, Haas TL, Marroncelli N, Patrizii M, Biffoni M et al. Antitumor effect of miR-197 targeting in p53 wild-type lung cancer. Cell Death Differ 2014; 21: 774-782.
78. Okada N, Lin CP, Ribeiro MC, Biton A, Lai G, He X et al. A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression. Genes Dev 2014; 28: 438-450.
79. Burns DM, D'Ambrogio A, Nottrott S, Richter JD. CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation. Nature 2011; 473: 105-108.
80. Fortunato O, Boeri M, Moro M, Verri C, Mensah M, Conte D et al. Mir-660 is downregulated in lung cancer patients and its replacement inhibits lung tumorigenesis by targeting MDM2-p53 interaction. Cell Death Dis 2014; 5: e1564.
81. Lezina L, Purmessur N, Antonov AV, Ivanova T, Karpova E, Krishan K et al. miR-16 and miR-26a target checkpoint kinases Wee1 and Chk1 in response to p53 activation by genotoxic stress. Cell Death Dis 2013; 4: e953.
82. Tucci P, Agostini M, Grespi F, Markert EK, Terrinoni A, Vousden KH et al. Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. Proc Natl Acad Sci USA 2012; 109: 15312-15317.
83. Zhang E, Yin D, Sun M, Kong R, Liu X, You L et al. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 2014; 5: e1243.
84. Ren Z-J, Nong X-Y, Lv Y-R, Sun H-H, An P-P, Wang F et al. Mir-509-5p joins the Mdm2/p53 feedback loop and regulates cancer cell growth. Cell Death Dis 2014; 5: e1387.
85. Gomes LR, Vessoni AT, Menck CFM. Three-dimensional microenvironment confers enhanced sensitivity to doxorubicin by reducing p53-dependent induction of autophagy. Oncogene 2015; 34: 5329-5340.
86. Simon HU, Yousefi S, Schmid I, Friis R. ATG5 can regulate p53 expression and activation. Cell Death Dis 2014; 5: e1339.
87. He Z, Liu H, Agostini M, Yousefi S, Perren A, Tschan MP et al. P73 regulates autophagy and hepatocellular lipid metabolism through a transcriptional activation of the ATG5 gene. Cell Death Differ 2013; 20: 1415-1424.
88. Garufi A, Pucci D, D'Orazi V, Cirone M, Bossi G, Avantaggiati ML et al. Degradation of mutant p53H175 protein by Zn(II) through autophagy. Cell Death Dis 2014; 5: e1271.
89. Ci Y, Shi K, An J, Yang Y, Hui K, Wu P et al. ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells. Cell Death Dis 2014; 5: e1542.
90. Rossi M, Rotblat B, Ansell K, Amelio I, Caraglia M, Misso G et al. High throughput screening for inhibitors of the HECT ubiquitin E3 ligase ITCH identifies antidepressant drugs as regulators of autophagy. Cell Death Dis 2014; 5: e1203.
91. Pant V, Lozano G. Limiting the power of p53 through the ubiquitin proteasome pathway. Genes Dev 2014; 28: 1739-1751.
92. Emerling BM, Hurov JB, Poulogiannis G, Tsukazawa KS, Choo-Wing R, Wulf GM et al. XDepletion of a putatively druggable class of phosphatidylinositol kinases inhibits growth of p53-Null tumors. Cell 2013; 155: 844-857.
93. Weilbacher A, Gutekunst M, Oren M, Aulitzky WE, van der Kuip H. RITA can induce cell death in p53-defective cells independently of p53 function via activation of JNK/SAPK and p38. Cell Death Dis 2014; 5: e1318.
94. Li H, Zhang Y, Ströse A, Tedesco D, Gurova K, Selivanova G. Integrated highthroughput analysis identifies Sp1 as a crucial determinant of p53-mediated apoptosis. Cell Death Differ 2014; 21: 1522-1534.
95. Kelly GL, Grabow S, Glaser SP, Fitzsimmons L, Aubrey BJ, Okamoto T et al. Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53. Genes Dev 2014; 28: 58-70.
96. Malatesta M, Peschiaroli A, Memmi EM, Zhang J, Antonov A, Green DR et al. The Cul4A-DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity. Oncogene 2012; 32: 4721-4726.
97. Fan Y-H, Cheng J, Vasudevan Sa, Dou J, Zhang H, Patel RH et al. USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis. Cell Death Dis 2013; 4: e867.
98. Zaccara S, Tebaldi T, Pederiva C, Ciribilli Y, Bisio A, Inga A. P53-directed translational control can shape and expand the universe of P53 target genes. Cell Death Differ 2014; 21: 1522-1534.
99. Brune M, Müller M, Melino G, Bierhaus A, Schilling T, Nawroth PP. Depletion of the receptor for advanced glycation end products (RAGE) sensitizes towards apoptosis via p53 and p73 posttranslational regulation. Oncogene 2012; 32: 1460-1468.
100. Han F, Liu W, Jiang X, Shi X, Yin L, Ao L et al. SOX30, a novel epigenetic silenced tumor suppressor, promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer. Oncogene 2014; 34: 4391-4402.
101. Link N, Kurtz P, O'Neal M, Garcia-Hughes G, Abrams JM. A p53 enhancer region regulates target genes through chromatin conformations in cis and in trans. Genes Dev 2013; 27: 2433-2438.
102. Saldaña-Meyer R, González-Buendía E, Guerrero G, Narendra V, Bonasio R, Recillas-Targa F et al. CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53. Genes Dev 2014; 28: 723-734.
103. Terrinoni A, Pagani IS, Zucchi I, Chiaravalli AM, Serra V, Rovera F et al. OTX1 expression in breast cancer is regulated by p53. Oncogene 2011; 30: 3096-3103.
104. Zambetti GP. Expanding the reach of the p53 tumor suppressor network. Cell Death Differ 2014; 21: 505-506.
105. Wang G, Fersht AR. Propagation of aggregated p53: cross-reaction and coaggregation vs. seeding. Proc Natl Acad Sci USA 2015; 112: 2443-2448.
106. Wang G, Fersht AR. Mechanism of initiation of aggregation of p53 revealed by φ-value analysis. Proc Natl Acad Sci USA 2015; 112: 2437-2442.
107. Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V et al. P53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene 2014; 34: 3605-3616.
108. Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS et al. Regulation of p53 activity through lysine methylation. Nature 2004; 432: 353-360.
109. Carr SM, Munro S, La Thangue NB. Lysine methylation and the regulation of p53. Essays Biochem 2012; 52: 79-92.
110. Koshland DE. Application of a Theory of Enzyme Specificity to Protein Synthesis. Proc Natl Acad Sci USA 1958; 44: 98-104.
111. Johnson KA. Role of induced fit in enzyme specificity: a molecular forward/reverse switch. J Biol Chem 2008; 283: 26297-26301.
112. Emamzadah S, Tropia L, Vincenti I, Falquet B, Halazonetis TD. Reversal of the DNA-binding-induced loop L1 conformational switch in an engineered human p53 protein. J Mol Biol 2014; 426: 936-944.
113. Oldfield CJ, Meng J, Yang JY, Yang MQ, Uversky VN, Dunker AK. Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners. BMC Genomics 2008; 9: S1.
114. Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 1993; 234: 779-815.
115. Kuszewski J, Gronenborn AM, Clore GM. Improving the packing and accuracy of NMR structures with a pseudopotential for the radius of gyration. J Am Chem Soc 1999; 121: 2337-2338.
116. Pronk S, Páll S, Schulz R, Larsson P, Bjelkmar P, Apostolov R et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 2013; 29: 845-854.
117. Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C. Comparison of multiple amber force fields and development of improved protein backbone parameters. Proteins Struct Funct Genet 2006; 65: 712-725.
118. Darden T, York D, Pedersen L. Particle mesh Ewald: an N log(N) method for Ewald sums in large systems. J Chem Phys 1993; 98: 10089.
119. Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983; 22: 2577-2637.
120. Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci USA 2001; 98: 10037-10041.
121. Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph 1996; 14: 33-38.