Modulation of the p53-MDM2 interaction by phosphorylation of Thr18: A computational study

Cell Cycle

Volumn 6, Issue 21, 2007, Pages 2604-2611

  Hui, Jun Lee ^a   Srinivasan, Deepa ^b   Coomber, David ^b   Lane, David P ^b   Verma, Chandra S ^a  

^a BIOINFORMATICS INSTITUTE   (Singapore)

^b INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Singapore)

Author keywords

Electrostatics; Helicity; MDM2; MDM4; p53; p53TAD; Phosphorylations

Indexed keywords

ASPARTIC ACID; LEUCINE; LYSINE; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P53; SERINE; THREONINE;

AMINO TERMINAL SEQUENCE; ARTICLE; BINDING AFFINITY; COMPLEX FORMATION; CRYSTAL STRUCTURE; GENE MUTATION; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR DYNAMICS; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; QUANTITATIVE ANALYSIS; REGULATORY MECHANISM; TRANSACTIVATION; WILD TYPE;

EID: 36849011121     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.6.21.4923     Document Type: Article

References (68)

1. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 253:49-53.
2. Harris CC. p53 Tumor suppressor gene: From the basic research laboratory to the clinic - An abridged historical perspective. Carcinogenesis 1996; 17:1187-98.
3. El-Deiry W. Regulation of p53 downstream genes. Semin Cancer Biol 1998; 8:345-57.
4. Webster GA, Perkins ND. Transcriptional cross talk between NF-kappaB and p53. Mol Cell Biol 1999; 19:3485-95.
5. Raman V, Martensen SA, Reisman D, Evron E, Odenwald WF, Jaffee E, Marks J, Sukumar S. Compromised HOXA5 function can limit p53 expression in human breast tumors. Nature 2000; 405:974-8.
6. Woods DB, Vousden KH. Regulation of p53 Function. Exp Cell Res 2001; 264:56-66.
7. Momand J, Wu HH, Dasgupta G. MDM2 - Master regulator of the p53 tumor suppressor protein. Genes 2000; 242:15-29.
8. Barak Y, Juven T, Haffner R, Oren M. Mdm2 expression is induced by wild type p53 activity. EMBO J 1993; 12:461-8.
9. Wu X, Bayle JH, Olson D, Levine AJ. The p53-mdm-2 autoregulatory feedback loop. Genes Dev 1993; 7:1126-36.
10. Shvarts A, Steegenga WT, Riteco N, van Laar T, Dekker P, Bazuine M, van Ham RC, van der Houven van Oordt W, Hateboer G, van der Eb AJ, Jochemsen AG. MDMX: A novel p53-binding protein with some functional properties of MDM2. EMBO J 1996; 15:5349-57.
11. Marine J, Jochemsen AG. Mdmx and Mdm2: Brothers in arms? Cell Cycle 2004; 3:900-4.
12. Stommel J, Wahl GM. A new twist in the feedback loop: Stress-activated MDM2 destabilization is required for p53 activation. Cell Cycle 2005; 4:411-7.
13. Ghosh M, Weghorst K, Berberich SJ. Mdmx inhibits ARF mediated Mdm2 sumoylation. Cell Cycle 2005; 4:604-8.
14. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP. Structure of the MDM2 oncoprotein bound to the p53 tumor supressor transactivation domain. Science 1996; 274:948-53.
15. Yu GW, Rudiger S, Veprintsev D, Freund S, Fernandez-Fernandez MR, Fersht AR. The central domain of HDM2 provides a second binding site for p53. Proc Natl Acad Sci USA 2006; 103:1227-32.
16. Lin J, Chen J, Elenbaas B, Levine AJ. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm2 and the adenovirus 5 E1B 55-kD protein. Genes Dev 1994; 8:1235-46.
17. Uesugi M, Verdine GL. The alpha-helical FXXPhi Phi motif in p53: TAF interaction and discrimination by MDM2. Proc Natl Acad Sci USA 1999; 96:14801-6.
18. Bottger V, Bottger A, Garcia-Echeverria C, Ramos YF, van der Eb AJ, Jochemsen AG, Lane DP. Comparative study of the p53-mdm2 and p53-MDMX interfaces. Oncogene 1999; 18:189-99.
19. Popowicz G, Czarna A, Rothweiler U, Szwagierczak A, Krajewski M, Holak T. Molecular basis for the inhibition of p53 by Mdmx. Cell Cycle 2007; 6, (In press).
20. Lees-Miller SP, Sakaguchi K, Ullrich SJ, Appella E, Anderson CW. Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53. Mol Cell Biol 1990; 12:5041-9.
21. Abraham RT. Cell cycle checkpoint signalling through the ATM and ATR kinases. Genes Dev 2001; 15:2177-96.
22. Dumaz N, Milne DM, Meek DW. Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15. FEBS Lett 1999; 463:312-6.
23. Hirao A, Kong YY, Matsuoka S, Wakeham A, Ruland J, Yoshida HD, Elledge SJ, Mak TW. DNA damage-inducible activation of p53 by the checkpoint kinase Chk2. Science 2000; 287:1824-7.
24. Shieh SY, Ahn J, Tamai K, Taya Y, Prives C. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 2000; 14:289-300.
25. Helt CE, Cliby WA, Keng PC, Bambara RA, O'Reilly MA. Ataxia telangiectasia mutated (ATM) and ATM and RAD3-related protein exhibit selective target specificities in response to different forms of DNA damage. J Biol Chem 2005; 280:1186-92.
26. Meek DW, Campbell LE, Jardine LJ, Knippschild U, McKendrick L, Milne DM. Multi-site phosphorylation of p53 by protein kinases inducible by p53 and DNA damage. Biochem Soc Trans 1997; 25:416-9.
27. Sakaguchi K, Saito S, Higashimoto Y, Roy S, Anderson CW, Appella E. Damage-mediated phosphorylation of human p53 threonine 18 through a cascade mediated by a casein 1-like kinase: Effect on Mdm2 binding. J Biol Chem 2000; 275:9278-83.
28. Dumaz N, Milne DM, Jardine LJ, Meek DW. Critical roles for the serine 20, but not the serine 15, phosphorylation site and for the polyproline domain in regulating p53 turnover. Biochem J 1999; 359:459-64.
29. Craig AL, Burch L, Vojtesek B, Mikutowska J, Thompson A, Hupp TR. Novel phosphorylation sites of human tumor suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of mdm2 (mouse double minute 2) protein are modified in human cancers. Biochem J 1999; 342:133-41.
30. Vega FM, Sevilla A, Lazo PA. p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol Cell Biol 2004; 24:10366-80.
31. Schon O, Friedler A, Bycroft M, Freund SMV, Fersht AR. Molecular mechanism of the interaction between MDM2 and p53. J Mol Biol 2002; 323:491-501.
32. Young MA, Gonfloni S, Superti-Furga G, Roux B, Kuriyan J. Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-Terminal Tyrosine phosphorylation. Cell 2001; 105:115-26.
33. Groban ES, Narayanan A, Jacobson MP. Conformational changes in protein loops and helices induced by post-translational phosphorylation. PLOS Comp Biol 2006; 2:238-50.
34. Lee H, Mok KH, Muhandiram R, Park KH, Suk JE, Kim DH, Chang J, Sung YC, Choi KY, Han KH. Local structural elements in the mostly unstructured transcriptional activation domain of human p53. J Biol Chem 2000; 275:29426-32.
35. Zondlo SC, Lee AE, Zondlo NJ. Determinants of specificity of MDM2 for the activation domains of p53 and p65: Proline27 disrupts the MDM2-binding motif of p53. Biochemistry 2006; 45:11945-57.
36. Bottger A, Bottger V, Garcia-Echeverria C, Chene P, Hochkeppel H, Sampson W, Ang K, Howard SF, Picksley SM, Lane DP. Molecular characterization of the HDM2-p53 interaction. J Mol Biol 1997; 269:744-56.
37. Shen TY, Wong CF, McCammon JA. Atomistic brownian dynamics simulation of peptide phosphorylation. J Am Chem Soc 2001; 123:9107-11.
38. Shen TY, Zong C, Hamelberg D, McCammon JA, Wolynes PG. The folding energy landscape and phosphorylation: Modeling the conformational switch of the NFAT regulatory domain. FASEB J 2005; 19:1389-95.
39. Rosal R, Pincus MR, Brandt-Rauf PW, Fine RL, Michl J, Wang H. NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells. Biochemistry 2004; 43:1854-61.
40. Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L, Lee M, Lee T, Duan Y, Wang Y, Donini O, Cieplak P, Srinivasan J, Case DA, Cheatham TE. Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Acc Chem Res 2000; 33:889-97.
41. Still WC, Tempczyk A, Hawley RC, Hendrickson T. Semianalytical treatment of solvation for molecular mechanics and dynamics. J Am Chem Soc 1990; 112:6127-9.
42. Reyes CM, Kollman PA. Structure and thermodynamics of RNA-protein binding: Using molecular dynamics and free energy analyses to calculate the free energies of binding and conformational change. J Mol Biol 2000; 297:1145-58.
43. Massova I, Kollman PA. Computational alanine scanning to probe protein-protein interactions: A novel approach to evaluate binding free energies. J Am Chem Soc 1999; 121:8133-43.
44. Zhong H, Carlson HA. Computational studies and peptidomimetic design for the human p53-MDM2 complex. Proteins 2005; 58:222-34.
45. Schon O, Friedler A, Freund S, Fersht AR. Binding of p53-derived ligands to MDM2 induces a variety of long range conformational changes. J Mol Biol 2004; 336:197-202.
46. Janin J. The kinetics of protein-protein recognition. PROTEINS 1997; 28:153-61.
47. 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; 98:10037-41.
48. Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicx KL, Calvo RR, Maguire D, Lattanze J, Franks CF, Zhao S, Ramachandren K, Bylebyl GR, Zhang M, Manthey CL, Petrella EC, Pantoliano MW, Deckman IC, Spurlino JC, Maroney AC, Tomczuk BE, Molloy CJ, Bone RF. Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. J Med Chem 2005; 48:909-12.
49. Selzer T, Albeck S, Schreiber G. Rational design of faster associating and tighter binding protein complexes. Nature Struct Biol 2000; 7:537-41.
50. Chandler DS, Singh RK, Caldwell LC, Bitler JL, Lozano G. Genotoxic stress induces coordinately regulated alternative splicing of the p53 modulators MDM2 and MDM4. Can Res 2006; 66.
51. Haines DS, Landers JE, Engle LJ, George DL. Physical and functional interaction between wild-type p53 and mdm2 proteins. Mol Cell Biol 1994; 14:1171-8.
52. Francoz S, Froment P, Bogaerts S, De Clercg S, Maetens M, Doumont G, Bellefroid E, Marine J. Mdm4 and Mdm2 coorperate to inhibit p53 activity in proliferating and quiescent cells in vivo. Proc Natl Acad Sci USA 2006; 103:3232-7.
53. Laurie N, Donovan S, Shih C, Zhang J, Mills N, Fuller C, Teunisse A, Lam S, Ramos Y, Mohan A, Johnson D, Wilson M, Rodriguez-Galindo C, Quarto M, Francoz S, Mendrysa S, Guy R, Marine J, Jochemsen AG, Dyer M. Inactivation of the p53 pathway in retinoblastoma. Nature 2006; 444:61-6.
54. Vriend G. WHAT IF: A molecular modeling and drug design program. J Mol Graph 1990; 8:52-6.
55. Case DA, Darden TA, Cheatham TE, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Wang B, Pearlman DA, Crowley M, Brozell S, Tsui V, Gohlke H, Mongan J, Hornak V, Cui G, Beroza P, Schafmeister C, Caldwell JW, Ross WS, Kollman PA. AMBER8. San Francisco: University of California, 2004.
56. Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc 1995; 117:5179-97.
57. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys 1983; 79:926-35.
58. van Gunsteren WF, Berendsen HJC. Algorithms for macromolecular dynamics and constraint dynamics. Mol Phys 1977; 34:1311-27.
59. Darden T, York D, Pedersen L. Particle mesh Ewald: An N.log(N) method for Ewald sums in large systems. J Chem Phys 1993; 98:10089-92.
60. Bashford D, Case DA. Generalized Born models of macromolecular solvation effects. Annu Rev Phys Chem 2000; 51:129-52.
61. Tsui V, Case DA. Molecular dynamics simulations of nucleic acids with a Generalized Born solvation model. J Am Chem Soc 2000; 122:2489-98.
62. Jayaram B, Sprous D, Beveridge DL. Solvation free energy of biomacromolecules: Parameters for a modified Generalized Born model consistent with the AMBER force field. J Phys Chem B 1998; 102:9571-6.
63. Connolly ML. Solvent-accessible surfaces of proteins and nucleic acids. Science 1983; 221:709-13.
64. Sanner MF, Olson AJ, Spehner JC. Reduced surface: An efficient way to compute molecular surfaces. Biopolymers 1996; 38:305-20.
65. Case DA. Normal-mode analysis of protein dynamics. Curr Opin Struct Biol 1994; 4:285-90.
66. Frishman D, Argos P. Knowledge-based protein secondary structure assignment. Proteins 1995; 23:566-79.
67. DeLano WL. The PyMOL molecular graphics system. San Carlos, CA, USA: DeLano Scientific, 2002.
68. Humphrey W, Dalke A, Schulten K. VMD-visual molecular dynamics. J Mol Graph 1996; 14:33-8.