4,081
Views
74
CrossRef citations to date
0
Altmetric
Review

The aggregation of mutant p53 produces prion-like properties in cancer

, , &
Pages 75-84 | Received 11 Dec 2013, Accepted 08 Jan 2014, Published online: 07 Feb 2014

References

  • Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature 1979; 278:261 - 3; http://dx.doi.org/10.1038/278261a0; PMID: 218111
  • Soto C. Prion hypothesis: the end of the controversy?. Trends Biochem Sci 2011; 36:151 - 8; http://dx.doi.org/10.1016/j.tibs.2010.11.001; PMID: 21130657
  • Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, Lashley T, Quinn NP, Rehncrona S, Björklund A, et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 2008; 14:501 - 3; http://dx.doi.org/10.1038/nm1746; PMID: 18391963
  • Grad LI, Guest WC, Yanai A, Pokrishevsky E, O’Neill MA, Gibbs E, Semenchenko V, Yousefi M, Wishart DS, Plotkin SS, et al. Intermolecular transmission of superoxide dismutase 1 misfolding in living cells. Proc Natl Acad Sci U S A 2011; 108:16398 - 403; http://dx.doi.org/10.1073/pnas.1102645108; PMID: 21930926
  • Ishimaru D, Maia LF, Maiolino LM, Quesado PA, Lopez PC, Almeida FC, Valente AP, Silva JL. Conversion of wild-type p53 core domain into a conformation that mimics a hot-spot mutant. J Mol Biol 2003; 333:443 - 51; http://dx.doi.org/10.1016/j.jmb.2003.08.026; PMID: 14529628
  • Ishimaru D, Andrade LR, Teixeira LS, Quesado PA, Maiolino LM, Lopez PM, Cordeiro Y, Costa LT, Heckl WM, Weissmüller G, et al. Fibrillar aggregates of the tumor suppressor p53 core domain. Biochemistry 2003; 42:9022 - 7; http://dx.doi.org/10.1021/bi034218k; PMID: 12885235
  • Silva JL, Vieira TC, Gomes MP, Bom AP, Lima LM, Freitas MS, Ishimaru D, Cordeiro Y, Foguel D. Ligand binding and hydration in protein misfolding: insights from studies of prion and p53 tumor suppressor proteins. Acc Chem Res 2010; 43:271 - 9; http://dx.doi.org/10.1021/ar900179t; PMID: 19817406
  • Ano Bom AP, Rangel LP, Costa DC, de Oliveira GA, Sanches D, Braga CA, Gava LM, Ramos CH, Cepeda AO, Stumbo AC, et al. Mutant p53 aggregates into prion-like amyloid oligomers and fibrils: implications for cancer. J Biol Chem 2012; 287:28152 - 62; http://dx.doi.org/10.1074/jbc.M112.340638; PMID: 22715097
  • Xu J, Reumers J, Couceiro JR, De Smet F, Gallardo R, Rudyak S, Cornelis A, Rozenski J, Zwolinska A, Marine JC, et al. Gain of function of mutant p53 by coaggregation with multiple tumor suppressors. Nat Chem Biol 2011; 7:285 - 95; http://dx.doi.org/10.1038/nchembio.546; PMID: 21445056
  • Wilcken R, Wang G, Boeckler FM, Fersht AR. Kinetic mechanism of p53 oncogenic mutant aggregation and its inhibition. Proc Natl Acad Sci U S A 2012; 109:13584 - 9; http://dx.doi.org/10.1073/pnas.1211550109; PMID: 22869713
  • Wang G, Fersht AR. First-order rate-determining aggregation mechanism of p53 and its implications. Proc Natl Acad Sci U S A 2012; 109:13590 - 5; http://dx.doi.org/10.1073/pnas.1211557109; PMID: 22869710
  • Lasagna-Reeves CA, Clos AL, Castillo-Carranza D, Sengupta U, Guerrero-Muñoz M, Kelly B, Wagner R, Kayed R. Dual role of p53 amyloid formation in cancer; loss of function and gain of toxicity. Biochem Biophys Res Commun 2013; 430:963 - 8; http://dx.doi.org/10.1016/j.bbrc.2012.11.130; PMID: 23261448
  • Forget KJ, Tremblay G, Roucou X. p53 Aggregates penetrate cells and induce the co-aggregation of intracellular p53. PLoS One 2013; 8:e69242; http://dx.doi.org/10.1371/journal.pone.0069242; PMID: 23844254
  • Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science 1982; 216:136 - 44; http://dx.doi.org/10.1126/science.6801762; PMID: 6801762
  • Bolton DC, McKinley MP, Prusiner SB. Identification of a protein that purifies with the scrapie prion. Science 1982; 218:1309 - 11; http://dx.doi.org/10.1126/science.6815801; PMID: 6815801
  • McKinley MP, Bolton DC, Prusiner SB. A protease-resistant protein is a structural component of the scrapie prion. Cell 1983; 35:57 - 62; http://dx.doi.org/10.1016/0092-8674(83)90207-6; PMID: 6414721
  • Basler K, Oesch B, Scott M, Westaway D, Wälchli M, Groth DF, McKinley MP, Prusiner SB, Weissmann C. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 1986; 46:417 - 28; http://dx.doi.org/10.1016/0092-8674(86)90662-8; PMID: 2873895
  • Chesebro B, Race R, Wehrly K, Nishio J, Bloom M, Lechner D, Bergstrom S, Robbins K, Mayer L, Keith JM, et al. Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature 1985; 315:331 - 3; http://dx.doi.org/10.1038/315331a0; PMID: 3923361
  • Riek R, Hornemann S, Wider G, Glockshuber R, Wüthrich K. NMR characterization of the full-length recombinant murine prion protein, mPrP(23-231). FEBS Lett 1997; 413:282 - 8; http://dx.doi.org/10.1016/S0014-5793(97)00920-4; PMID: 9280298
  • Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhorn I, Huang Z, Fletterick RJ, Cohen FE, et al. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A 1993; 90:10962 - 6; http://dx.doi.org/10.1073/pnas.90.23.10962; PMID: 7902575
  • Telling GC, Parchi P, DeArmond SJ, Cortelli P, Montagna P, Gabizon R, Mastrianni J, Lugaresi E, Gambetti P, Prusiner SB. Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science 1996; 274:2079 - 82; http://dx.doi.org/10.1126/science.274.5295.2079; PMID: 8953038
  • Kocisko DA, Come JH, Priola SA, Chesebro B, Raymond GJ, Lansbury PT, Caughey B. Cell-free formation of protease-resistant prion protein. Nature 1994; 370:471 - 4; http://dx.doi.org/10.1038/370471a0; PMID: 7913989
  • Kocisko DA, Priola SA, Raymond GJ, Chesebro B, Lansbury PT Jr., Caughey B. Species specificity in the cell-free conversion of prion protein to protease-resistant forms: a model for the scrapie species barrier. Proc Natl Acad Sci U S A 1995; 92:3923 - 7; http://dx.doi.org/10.1073/pnas.92.9.3923; PMID: 7732006
  • McKinley MP, Braunfeld MB, Bellinger CG, Prusiner SB. Molecular characteristics of prion rods purified from scrapie-infected hamster brains. J Infect Dis 1986; 154:110 - 20; http://dx.doi.org/10.1093/infdis/154.1.110; PMID: 2872252
  • Merz PA, Somerville RA, Wisniewski HM, Manuelidis L, Manuelidis EE. Scrapie-associated fibrils in Creutzfeldt-Jakob disease. Nature 1983; 306:474 - 6; http://dx.doi.org/10.1038/306474a0; PMID: 6358899
  • Griffith JS. Self-replication and scrapie. Nature 1967; 215:1043 - 4; http://dx.doi.org/10.1038/2151043a0; PMID: 4964084
  • Jarrett JT, Lansbury PT Jr.. Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie?. Cell 1993; 73:1055 - 8; http://dx.doi.org/10.1016/0092-8674(93)90635-4; PMID: 8513491
  • Cordeiro Y, Machado F, Juliano L, Juliano MA, Brentani RR, Foguel D, Silva JL. DNA converts cellular prion protein into the beta-sheet conformation and inhibits prion peptide aggregation. J Biol Chem 2001; 276:49400 - 9; http://dx.doi.org/10.1074/jbc.M106707200; PMID: 11604397
  • Supattapone S, Deleault NR, Rees JR. Amplification of purified prions in vitro. Methods Mol Biol 2008; 459:117 - 30; http://dx.doi.org/10.1007/978-1-59745-234-2_9; PMID: 18576152
  • Silva JL, Lima LM, Foguel D, Cordeiro Y. Intriguing nucleic-acid-binding features of mammalian prion protein. Trends Biochem Sci 2008; 33:132 - 40; http://dx.doi.org/10.1016/j.tibs.2007.11.003; PMID: 18243708
  • Vieira TC, Reynaldo DP, Gomes MP, Almeida MS, Cordeiro Y, Silva JL. Heparin binding by murine recombinant prion protein leads to transient aggregation and formation of RNA-resistant species. J Am Chem Soc 2011; 133:334 - 44; http://dx.doi.org/10.1021/ja106725p; PMID: 21142149
  • Crespo R, Rocha FA, Damas AM, Martins PM. A generic crystallization-like model that describes the kinetics of amyloid fibril formation. J Biol Chem 2012; 287:30585 - 94; http://dx.doi.org/10.1074/jbc.M112.375345; PMID: 22767606
  • Condeelis J. How is actin polymerization nucleated in vivo?. Trends Cell Biol 2001; 11:288 - 93; http://dx.doi.org/10.1016/S0962-8924(01)02008-6; PMID: 11413039
  • Job D, Valiron O, Oakley B. Microtubule nucleation. Curr Opin Cell Biol 2003; 15:111 - 7; http://dx.doi.org/10.1016/S0955-0674(02)00003-0; PMID: 12517712
  • Vendruscolo M, Knowles TP, Dobson CM. Protein solubility and protein homeostasis: a generic view of protein misfolding disorders. Cold Spring Harb Perspect Biol 2011; 3:a010454; http://dx.doi.org/10.1101/cshperspect.a010454; PMID: 21825020
  • Petkova AT, Leapman RD, Guo Z, Yau WM, Mattson MP, Tycko R. Self-propagating, molecular-level polymorphism in Alzheimer’s beta-amyloid fibrils. Science 2005; 307:262 - 5; http://dx.doi.org/10.1126/science.1105850; PMID: 15653506
  • Ma J, Wollmann R, Lindquist S. Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol. Science 2002; 298:1781 - 5; http://dx.doi.org/10.1126/science.1073725; PMID: 12386337
  • Rosen RF, Fritz JJ, Dooyema J, Cintron AF, Hamaguchi T, Lah JJ, LeVine H 3rd, Jucker M, Walker LC. Exogenous seeding of cerebral β-amyloid deposition in βAPP-transgenic rats. J Neurochem 2012; 120:660 - 6; http://dx.doi.org/10.1111/j.1471-4159.2011.07551.x; PMID: 22017494
  • Furukawa Y, Kaneko K, Watanabe S, Yamanaka K, Nukina N. A seeding reaction recapitulates intracellular formation of Sarkosyl-insoluble transactivation response element (TAR) DNA-binding protein-43 inclusions. J Biol Chem 2011; 286:18664 - 72; http://dx.doi.org/10.1074/jbc.M111.231209; PMID: 21454603
  • Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 2009; 11:909 - 13; http://dx.doi.org/10.1038/ncb1901; PMID: 19503072
  • Plouffe V, Mohamed NV, Rivest-McGraw J, Bertrand J, Lauzon M, Leclerc N. Hyperphosphorylation and cleavage at D421 enhance tau secretion. PLoS One 2012; 7:e36873; http://dx.doi.org/10.1371/journal.pone.0036873; PMID: 22615831
  • Kfoury N, Holmes BB, Jiang H, Holtzman DM, Diamond MI. Trans-cellular propagation of Tau aggregation by fibrillar species. J Biol Chem 2012; 287:19440 - 51; http://dx.doi.org/10.1074/jbc.M112.346072; PMID: 22461630
  • Aguzzi A, Rajendran L. The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 2009; 64:783 - 90; http://dx.doi.org/10.1016/j.neuron.2009.12.016; PMID: 20064386
  • Zhang B, Une Y, Fu X, Yan J, Ge F, Yao J, Sawashita J, Mori M, Tomozawa H, Kametani F, et al. Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease. Proc Natl Acad Sci U S A 2008; 105:7263 - 8; http://dx.doi.org/10.1073/pnas.0800367105; PMID: 18474855
  • Levy CB, Stumbo AC, Ano Bom AP, Portari EA, Cordeiro Y, Silva JL, De Moura-Gallo CV. Co-localization of mutant p53 and amyloid-like protein aggregates in breast tumors. Int J Biochem Cell Biol 2011; 43:60 - 4; http://dx.doi.org/10.1016/j.biocel.2010.10.017; PMID: 21056685
  • Blanco LP, Evans ML, Smith DR, Badtke MP, Chapman MR. Diversity, biogenesis and function of microbial amyloids. Trends Microbiol 2012; 20:66 - 73; http://dx.doi.org/10.1016/j.tim.2011.11.005; PMID: 22197327
  • Si K, Lindquist S, Kandel ER. A neuronal isoform of the aplysia CPEB has prion-like properties. Cell 2003; 115:879 - 91; http://dx.doi.org/10.1016/S0092-8674(03)01020-1; PMID: 14697205
  • Stefani M, Dobson CM. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J Mol Med (Berl) 2003; 81:678 - 99; http://dx.doi.org/10.1007/s00109-003-0464-5; PMID: 12942175
  • Joerger AC, Fersht AR. Structural biology of the tumor suppressor p53. Annu Rev Biochem 2008; 77:557 - 82; http://dx.doi.org/10.1146/annurev.biochem.77.060806.091238; PMID: 18410249
  • Chin KV, Ueda K, Pastan I, Gottesman MM. Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Science 1992; 255:459 - 62; http://dx.doi.org/10.1126/science.1346476; PMID: 1346476
  • Freed-Pastor WA, Prives C. Mutant p53: one name, many proteins. Genes Dev 2012; 26:1268 - 86; http://dx.doi.org/10.1101/gad.190678.112; PMID: 22713868
  • Muller PA, Vousden KH. p53 mutations in cancer. Nat Cell Biol 2013; 15:2 - 8; http://dx.doi.org/10.1038/ncb2641; PMID: 23263379
  • Gualberto A, Aldape K, Kozakiewicz K, Tlsty TD. An oncogenic form of p53 confers a dominant, gain-of-function phenotype that disrupts spindle checkpoint control. Proc Natl Acad Sci U S A 1998; 95:5166 - 71; http://dx.doi.org/10.1073/pnas.95.9.5166; PMID: 9560247
  • Chan WM, Siu WY, Lau A, Poon RY. How many mutant p53 molecules are needed to inactivate a tetramer?. Mol Cell Biol 2004; 24:3536 - 51; http://dx.doi.org/10.1128/MCB.24.8.3536-3551.2004; PMID: 15060172
  • Silva JL, Rangel LP, Costa DC, Cordeiro Y, De Moura Gallo CV. Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor. Biosci Rep 2013; 33:e00054; http://dx.doi.org/10.1042/BSR20130065; PMID: 24003888
  • Irwin MS, Kaelin WG Jr.. Role of the newer p53 family proteins in malignancy. Apoptosis 2001; 6:17 - 29; http://dx.doi.org/10.1023/A:1009663809458; PMID: 11321038
  • Neilsen PM, Noll JE, Suetani RJ, Schulz RB, Al-Ejeh F, Evdokiou A, Lane DP, Callen DF. Mutant p53 uses p63 as a molecular chaperone to alter gene expression and induce a pro-invasive secretome. Oncotarget 2011; 2:1203 - 17; PMID: 22203497
  • Martynova E, Pozzi S, Basile V, Dolfini D, Zambelli F, Imbriano C, Pavesi G, Mantovani R. Gain-of-function p53 mutants have widespread genomic locations partially overlapping with p63. Oncotarget 2012; 3:132 - 43; PMID: 22361592
  • Strano S, Fontemaggi G, Costanzo A, Rizzo MG, Monti O, Baccarini A, Del Sal G, Levrero M, Sacchi A, Oren M, et al. Physical interaction with human tumor-derived p53 mutants inhibits p63 activities. J Biol Chem 2002; 277:18817 - 26; http://dx.doi.org/10.1074/jbc.M201405200; PMID: 11893750
  • Lee AS, Galea C, DiGiammarino EL, Jun B, Murti G, Ribeiro RC, Zambetti G, Schultz CP, Kriwacki RW. Reversible amyloid formation by the p53 tetramerization domain and a cancer-associated mutant. J Mol Biol 2003; 327:699 - 709; http://dx.doi.org/10.1016/S0022-2836(03)00175-X; PMID: 12634062
  • Rigacci S, Bucciantini M, Relini A, Pesce A, Gliozzi A, Berti A, Stefani M. The (1-63) region of the p53 transactivation domain aggregates in vitro into cytotoxic amyloid assemblies. Biophys J 2008; 94:3635 - 46; http://dx.doi.org/10.1529/biophysj.107.122283; PMID: 18199664
  • Fernandez-Escamilla AM, Rousseau F, Schymkowitz J, Serrano L. Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins. Nat Biotechnol 2004; 22:1302 - 6; http://dx.doi.org/10.1038/nbt1012; PMID: 15361882
  • Hamodrakas SJ. Protein aggregation and amyloid fibril formation prediction software from primary sequence: towards controlling the formation of bacterial inclusion bodies. FEBS J 2011; 278:2428 - 35; http://dx.doi.org/10.1111/j.1742-4658.2011.08164.x; PMID: 21569208
  • Conchillo-Solé O, de Groot NS, Avilés FX, Vendrell J, Daura X, Ventura S. AGGRESCAN: a server for the prediction and evaluation of “hot spots” of aggregation in polypeptides. BMC Bioinformatics 2007; 8:65; http://dx.doi.org/10.1186/1471-2105-8-65; PMID: 17324296
  • Oliveberg M. Waltz, an exciting new move in amyloid prediction. Nat Methods. United States, 2010:187-8.
  • Tartaglia GG, Vendruscolo M. The Zyggregator method for predicting protein aggregation propensities. Chem Soc Rev 2008; 37:1395 - 401; http://dx.doi.org/10.1039/b706784b; PMID: 18568165
  • Milner J, Medcalf EA. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell 1991; 65:765 - 74; http://dx.doi.org/10.1016/0092-8674(91)90384-B; PMID: 2040013
  • Antony H, Wiegmans AP, Wei MQ, Chernoff YO, Khanna KK, Munn AL. Potential roles for prions and protein-only inheritance in cancer. Cancer Metastasis Rev 2012; 31:1 - 19; http://dx.doi.org/10.1007/s10555-011-9325-9; PMID: 22138778
  • Latonen L, Moore HM, Bai B, Jäämaa S, Laiho M. Proteasome inhibitors induce nucleolar aggregation of proteasome target proteins and polyadenylated RNA by altering ubiquitin availability. Oncogene 2011; 30:790 - 805; http://dx.doi.org/10.1038/onc.2010.469; PMID: 20956947
  • Lee SY, Jeong EK, Jeon HM, Kim CH, Kang HS. Implication of necrosis-linked p53 aggregation in acquired apoptotic resistance to 5-FU in MCF-7 multicellular tumour spheroids. Oncol Rep 2010; 24:73 - 9; PMID: 20514446
  • Wiech M, Olszewski MB, Tracz-Gaszewska Z, Wawrzynow B, Zylicz M, Zylicz A. Molecular mechanism of mutant p53 stabilization: the role of HSP70 and MDM2. PLoS One 2012; 7:e51426; http://dx.doi.org/10.1371/journal.pone.0051426; PMID: 23251530
  • Kirilyuk A, Shimoji M, Catania J, Sahu G, Pattabiraman N, Giordano A, Albanese C, Mocchetti I, Toretsky JA, Uversky VN, et al. An intrinsically disordered region of the acetyltransferase p300 with similarity to prion-like domains plays a role in aggregation. PLoS One 2012; 7:e48243; http://dx.doi.org/10.1371/journal.pone.0048243; PMID: 23133622
  • Nieva J, Song BD, Rogel JK, Kujawara D, Altobel L 3rd, Izharrudin A, Boldt GE, Grover RK, Wentworth AD, Wentworth P Jr.. Cholesterol secosterol aldehydes induce amyloidogenesis and dysfunction of wild-type tumor protein p53. Chem Biol 2011; 18:920 - 7; http://dx.doi.org/10.1016/j.chembiol.2011.02.018; PMID: 21802012
  • Ishimaru D, Ano Bom AP, Lima LM, Quesado PA, Oyama MF, de Moura Gallo CV, Cordeiro Y, Silva JL. Cognate DNA stabilizes the tumor suppressor p53 and prevents misfolding and aggregation. Biochemistry 2009; 48:6126 - 35; http://dx.doi.org/10.1021/bi9003028; PMID: 19505151
  • Lyubchenko YL, Shlyakhtenko LS, Nagaich A, Appella E, Harrington RE, Lindsay SM. Polymerization of the dna binding fragment of p53 on dna: atomic force microscopy study. Scanning Microsc 1998; 12:455 - 63
  • Riley KJ, James Maher L 3rd. Analysis of p53-RNA interactions in cultured human cells. Biochem Biophys Res Commun 2007; 363:381 - 7; http://dx.doi.org/10.1016/j.bbrc.2007.08.181; PMID: 17869221
  • Samad A, Carroll RB. The tumor suppressor p53 is bound to RNA by a stable covalent linkage. Mol Cell Biol 1991; 11:1598 - 606; PMID: 1705009
  • Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Yoshida T, Itoh H, Kohno K. Binding of RNA to p53 regulates its oligomerization and DNA-binding activity. Oncogene 2004; 23:4371 - 9; http://dx.doi.org/10.1038/sj.onc.1207583; PMID: 15064727
  • Zanzoni A, Marchese D, Agostini F, Bolognesi B, Cirillo D, Botta-Orfila M, Livi CM, Rodriguez-Mulero S, Tartaglia GG. Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein. Nucleic Acids Res 2013; 41:9987 - 98; http://dx.doi.org/10.1093/nar/gkt794; PMID: 24003031
  • Chemes LB, Noval MG, Sánchez IE, de Prat-Gay G. Folding of a cyclin box: linking multitarget binding to marginal stability, oligomerization, and aggregation of the retinoblastoma tumor suppressor AB pocket domain. J Biol Chem 2013; 288:18923 - 38; http://dx.doi.org/10.1074/jbc.M113.467316; PMID: 23632018
  • Sebastian S, Azzariti A, Silvestris N, Porcelli L, Russo A, Paradiso A. p53 as the main traffic controller of the cell signaling network. [Landmark Ed] Front Biosci (Landmark Ed) 2010; 15:1172 - 90; http://dx.doi.org/10.2741/3669; PMID: 20515749
  • Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature 2000; 408:307 - 10; http://dx.doi.org/10.1038/35042675; PMID: 11099028
  • Giannakakou P, Sackett DL, Ward Y, Webster KR, Blagosklonny MV, Fojo T. p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Nat Cell Biol 2000; 2:709 - 17; http://dx.doi.org/10.1038/35036335; PMID: 11025661
  • Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J 1999; 18:1660 - 72; http://dx.doi.org/10.1093/emboj/18.6.1660; PMID: 10075936
  • Zhang T, Prives C. Cyclin a-CDK phosphorylation regulates MDM2 protein interactions. J Biol Chem 2001; 276:29702 - 10; http://dx.doi.org/10.1074/jbc.M011326200; PMID: 11359766
  • Freedman DA, Wu L, Levine AJ. Functions of the MDM2 oncoprotein. Cell Mol Life Sci 1999; 55:96 - 107; http://dx.doi.org/10.1007/s000180050273; PMID: 10065155
  • Higashimoto Y, Asanomi Y, Takakusagi S, Lewis MS, Uosaki K, Durell SR, Anderson CW, Appella E, Sakaguchi K. Unfolding, aggregation, and amyloid formation by the tetramerization domain from mutant p53 associated with lung cancer. Biochemistry 2006; 45:1608 - 19; http://dx.doi.org/10.1021/bi051192j; PMID: 16460008
  • Moll UM, Ostermeyer AG, Haladay R, Winkfield B, Frazier M, Zambetti G. Cytoplasmic sequestration of wild-type p53 protein impairs the G1 checkpoint after DNA damage. Mol Cell Biol 1996; 16:1126 - 37; PMID: 8622657
  • Seyhan AA. RNAi: a potential new class of therapeutic for human genetic disease. Hum Genet 2011; 130:583 - 605; http://dx.doi.org/10.1007/s00439-011-0995-8; PMID: 21537948
  • Martinez LA, Naguibneva I, Lehrmann H, Vervisch A, Tchénio T, Lozano G, Harel-Bellan A. Synthetic small inhibiting RNAs: efficient tools to inactivate oncogenic mutations and restore p53 pathways. Proc Natl Acad Sci U S A 2002; 99:14849 - 54; http://dx.doi.org/10.1073/pnas.222406899; PMID: 12403821
  • Tanaka K, Matsuda N. Proteostasis and neurodegeneration: The roles of proteasomal degradation and autophagy. Biochim Biophys Acta 2014; 1843:197 - 204; http://dx.doi.org/10.1016/j.bbamcr.2013.03.012; PMID: 23523933
  • Rubinsztein DC, Codogno P, Levine B. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 2012; 11:709 - 30; http://dx.doi.org/10.1038/nrd3802; PMID: 22935804
  • Ferraz da Costa DC, Casanova FA, Quarti J, Malheiros MS, Sanches D, Dos Santos PS, Fialho E, Silva JL. Transient transfection of a wild-type p53 gene triggers resveratrol-induced apoptosis in cancer cells. PLoS One 2012; 7:e48746; http://dx.doi.org/10.1371/journal.pone.0048746; PMID: 23152798
  • Kaufman SK, Diamond MI. Prion-like propagation of protein aggregation and related therapeutic strategies. Neurotherapeutics 2013; 10:371 - 82; http://dx.doi.org/10.1007/s13311-013-0196-3; PMID: 23801258
  • Lin Y, Benchimol S. Cytokines inhibit p53-mediated apoptosis but not p53-mediated G1 arrest. Mol Cell Biol 1995; 15:6045 - 54; PMID: 7565757
  • Riou G, Barrois M, Prost S, Terrier MJ, Theodore C, Levine AJ. The p53 and mdm-2 genes in human testicular germ-cell tumors. Mol Carcinog 1995; 12:124 - 31; http://dx.doi.org/10.1002/mc.2940120303; PMID: 7893365
  • Chen F, Wang W, El-Deiry WS. Current strategies to target p53 in cancer. Biochem Pharmacol 2010; 80:724 - 30; http://dx.doi.org/10.1016/j.bcp.2010.04.031; PMID: 20450892
  • Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP. Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer 2009; 9:862 - 73; http://dx.doi.org/10.1038/nrc2763; PMID: 19935675
  • Chène P. Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer 2003; 3:102 - 9; http://dx.doi.org/10.1038/nrc991; PMID: 12563309
  • Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, Selivanova G. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 2004; 10:1321 - 8; http://dx.doi.org/10.1038/nm1146; PMID: 15558054
  • Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303:844 - 8; http://dx.doi.org/10.1126/science.1092472; PMID: 14704432
  • Lambert JM, Gorzov P, Veprintsev DB, Söderqvist M, Segerbäck D, Bergman J, Fersht AR, Hainaut P, Wiman KG, Bykov VJ. PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell 2009; 15:376 - 88; http://dx.doi.org/10.1016/j.ccr.2009.03.003; PMID: 19411067
  • Bykov VJ, Issaeva N, Zache N, Shilov A, Hultcrantz M, Bergman J, Selivanova G, Wiman KG. Reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs. J Biol Chem 2005; 280:30384 - 91; http://dx.doi.org/10.1074/jbc.M501664200; PMID: 15998635
  • Kravchenko JE, Ilyinskaya GV, Komarov PG, Agapova LS, Kochetkov DV, Strom E, Frolova EI, Kovriga I, Gudkov AV, Feinstein E, et al. Small-molecule RETRA suppresses mutant p53-bearing cancer cells through a p73-dependent salvage pathway. Proc Natl Acad Sci U S A 2008; 105:6302 - 7; http://dx.doi.org/10.1073/pnas.0802091105; PMID: 18424558
  • Selivanova G, Iotsova V, Okan I, Fritsche M, Ström M, Groner B, Grafström RC, Wiman KG. Restoration of the growth suppression function of mutant p53 by a synthetic peptide derived from the p53 C-terminal domain. Nat Med 1997; 3:632 - 8; http://dx.doi.org/10.1038/nm0697-632; PMID: 9176489
  • Kim AL, Raffo AJ, Brandt-Rauf PW, Pincus MR, Monaco R, Abarzua P, Fine RL. Conformational and molecular basis for induction of apoptosis by a p53 C-terminal peptide in human cancer cells. J Biol Chem 1999; 274:34924 - 31; http://dx.doi.org/10.1074/jbc.274.49.34924; PMID: 10574967
  • Liu X, Wilcken R, Joerger AC, Chuckowree IS, Amin J, Spencer J, Fersht AR. Small molecule induced reactivation of mutant p53 in cancer cells. Nucleic Acids Res 2013; 41:6034 - 44; http://dx.doi.org/10.1093/nar/gkt305; PMID: 23630318