Acetylation of Lysine 382 and Phosphorylation of Serine 392 in p53 Modulate the Interaction between p53 and MDC1 In Vitro

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Shahar, Or David ^a   Gabizon, Ronen ^a   Feine, Oren ^a   Alhadeff, Raphael ^a   Ganoth, Assaf ^b,c   Argaman, Liron ^a   Shimshoni, Elee ^a   Friedler, Assaf ^a   Goldberg, Michal ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b INTERDISCIPLINARY CENTER   (Israel)

^c UNIVERSITY OF HAIFA   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

LYSINE; NUCLEAR PROTEIN; PROTEIN MDC1; PROTEIN P53; SERINE; UNCLASSIFIED DRUG; MDC1 PROTEIN, HUMAN; TRANSACTIVATOR PROTEIN;

ACETYLATION; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELLULAR STRESS RESPONSE; CONTROLLED STUDY; DNA DAMAGE; HUMAN; HUMAN CELL; IN VITRO STUDY; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; METABOLISM; PHOSPHORYLATION; PROTEIN CONFORMATION;

ACETYLATION; DNA DAMAGE; HUMANS; IN VITRO TECHNIQUES; LYSINE; MODELS, MOLECULAR; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN CONFORMATION; SERINE; TRANS-ACTIVATORS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84886004895     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0078472     Document Type: Article

References (83)

1. Lord CJ, Ashworth A, (2012) The DNA damage response and cancer therapy. Nature 481: 287-294. doi:10.1038/nature10760. PubMed: 22258607.
2. Harrison JC, Haber JE, (2006) Surviving the breakup: the DNA damage checkpoint. Annu Rev Genet 40: 209-235. doi:10.1146/annurev.genet.40.051206.105231. PubMed: 16805667.
3. van den Bosch M, Bree RT, Lowndes NF, (2003) The MRN complex: coordinating and mediating the response to broken chromosomes. EMBO Rep 4: 844-849. doi:10.1038/sj.embor.embor925. PubMed: 12949583.
4. Canman CE, (2003) Checkpoint mediators: relaying signals from DNA strand breaks. Curr Biol 13: R488-R490. doi:10.1016/S0960-9822(03)00410-X. PubMed: 12814569.
5. Bradbury JM, Jackson SP, (2003) The complex matter of DNA double-strand break detection. Biochem Soc Trans 31: 40-44. PubMed: 12546650.
6. Adams MM, Carpenter PB, (2006) Tying the loose ends together in DNA double strand break repair with 53BP1. Cell Div: 1: 19. PubMed: 16945145.
7. Lukas J, Lukas C, Bartek J, (2011) More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol 13: 1161-1169. doi:10.1038/ncb2344. PubMed: 21968989.
8. Santos-Rosa H, Caldas C, (2005) Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 41: 2381-2402. doi:10.1016/j.ejca.2005.08.010. PubMed: 16226460.
9. van Attikum H, Gasser SM, (2009) Crosstalk between histone modifications during the DNA damage response. Trends Cell Biol 19: 207-217. doi:10.1016/j.tcb.2009.03.001. PubMed: 19342239.
10. Beneke S, (2012) Regulation of chromatin structure by poly(ADP-ribosyl)ation. Front Genet 3: 169. PubMed: 22969794.
11. Joerger AC, Fersht AR, (2007) Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene 26: 2226-2242. doi:10.1038/sj.onc.1210291. PubMed: 17401432.
12. Ryan KM, Phillips AC, Vousden KH, (2001) Regulation and function of the p53 tumor suppressor protein. Curr Opin Cell Biol 13: 332-337. doi:10.1016/S0955-0674(00)00216-7. PubMed: 11343904.
13. Vogelstein B, Lane D, Levine AJ, (2000) Surfing the p53 network. Nature 408: 307-310. doi:10.1038/35042675. PubMed: 11099028.
14. Toledo F, Wahl GM, (2006) Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 6: 909-923. doi:10.1038/nrc2012. PubMed: 17128209.
15. Vousden KH, Prives C, (2009) Blinded by the Light: The Growing Complexity of p53. Cell 137: 413-431. doi:10.1016/j.cell.2009.04.037. PubMed: 19410540.
16. Jenkins LM, Durell SR, Mazur SJ, Appella E, (2012) p53 N-terminal phosphorylation: a defining layer of complex regulation. Carcinogenesis 33: 1441-1449. doi:10.1093/carcin/bgs145. PubMed: 22505655.
17. Berger M, Vogt Sionov R, Levine AJ, Haupt Y, (2001) A role for the polyproline domain of p53 in its regulation by Mdm2. J Biol Chem 276: 3785-3790. doi:10.1074/jbc.M008879200. PubMed: 11053443.
18. el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B, (1992) Definition of a consensus binding site for p53. Nat Genet 1: 45-49. doi:10.1038/ng0492-45. PubMed: 1301998.
19. Chène P, (2001) The role of tetramerization in p53 function. Oncogene 20: 2611-2617. doi:10.1038/sj.onc.1204373. PubMed: 11420672.
20. Ahn J, Prives C, (2001) The C-terminus of p53: the more you learn the less you know. Nat Struct Biol 8: 730-732. doi:10.1038/nsb0901-730. PubMed: 11524665.
21. Wade M, Wang YV, Wahl GM, (2010) The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol 20: 299-309. doi:10.1016/j.tcb.2010.01.009. PubMed: 20172729.
22. Gu B, Zhu WG, (2012) Surf the post-translational modification network of p53 regulation. Int J Biol Sci 8: 672-684. PubMed: 22606048.
23. Dai C, Gu W, (2010) p53 post-translational modification: deregulated in tumorigenesis. Trends Mol Med 16: 528-536. doi:10.1016/j.molmed.2010.09.002. PubMed: 20932800.
24. Giaccia AJ, Kastan MB, (1998) The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 12: 2973-2983. doi:10.1101/gad.12.19.2973. PubMed: 9765199.
25. Anderson ME, Woelker B, Reed M, Wang P, Tegtmeyer P, (1997) Reciprocal interference between the sequence-specific core and nonspecific C-terminal DNA binding domains of p53: implications for regulation. Mol Cell Biol 17: 6255-6264. PubMed: 9343386.
26. Bayle JH, Elenbaas B, Levine AJ, (1995) The carboxyl-terminal domain of the p53 protein regulates sequence-specific DNA binding through its nonspecific nucleic acid-binding activity. Proc Natl Acad Sci U S A 92: 5729-5733. doi:10.1073/pnas.92.12.5729. PubMed: 7777576.
27. Hupp TR, Lane DP, (1994) Allosteric activation of latent p53 tetramers. Curr Biol 4: 865-875. doi:10.1016/S0960-9822(00)00195-0. PubMed: 7850419.
28. Hupp TR, Meek DW, Midgley CA, Lane DP, (1993) Activation of the cryptic DNA binding function of mutant forms of p53. Nucleic Acids Res 21: 3167-3174. doi:10.1093/nar/21.14.3167. PubMed: 8341590.
29. Hupp TR, Sparks A, Lane DP, (1995) Small peptides activate the latent sequence-specific DNA binding function of p53. Cell 83: 237-245. doi:10.1016/0092-8674(95)90165-5. PubMed: 7585941.
30. Sakaguchi K, Sakamoto H, Lewis MS, Anderson CW, Erickson JW, et al. (1997) Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry 36: 10117-10124. doi:10.1021/bi970759w. PubMed: 9254608.
31. Sakaguchi K, Sakamoto H, Xie D, Erickson JW, Lewis MS, et al. (1997) Effect of phosphorylation on tetramerization of the tumor suppressor protein p53. J Protein Chem 16: 553-556. doi:10.1023/A:1026334116189. PubMed: 9246643.
32. Gu W, Roeder RG, (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90: 595-606. doi:10.1016/S0092-8674(00)80521-8. PubMed: 9288740.
33. Friedler A, Veprintsev DB, Rutherford T, von Glos KI, Fersht AR, (2005) Binding of Rad51 and other peptide sequences to a promiscuous, highly electrostatic binding site in p53. J Biol Chem 280: 8051-8059. PubMed: 15611070.
34. Goldberg M, Stucki M, Falck J, D'Amours D, Rahman D, et al. (2003) MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421: 952-956. doi:10.1038/nature01445. PubMed: 12607003.
35. Lou Z, Chini CC, Minter-Dykhouse K, Chen J, (2003) Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. J Biol Chem 278: 13599-13602. doi:10.1074/jbc.C300060200. PubMed: 12611903.
36. Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ, (2003) MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 421: 961-966. doi:10.1038/nature01446. PubMed: 12607005.
37. Xu X, Stern DF, (2003) NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors. FASEB J 17: 1842-1848. doi:10.1096/fj.03-0310com. PubMed: 14519663.
38. Lou Z, Chen BP, Asaithamby A, Minter-Dykhouse K, Chen DJ, et al. (2004) MDC1 regulates DNA-PK autophosphorylation in response to DNA damage. J Biol Chem 279: 46359-46362. doi:10.1074/jbc.C400375200. PubMed: 15377652.
39. Dimitrova N, de Lange T, (2006) MDC1 accelerates nonhomologous end-joining of dysfunctional telomeres. Genes Dev 20: 3238-3243. doi:10.1101/gad.1496606. PubMed: 17158742.
40. Zhang J, Ma Z, Treszezamsky A, Powell SN, (2005) MDC1 interacts with Rad51 and facilitates homologous recombination. Nat Struct Mol Biol 12: 902-909. doi:10.1038/nsmb991. PubMed: 16186822.
41. Xie A, Hartlerode A, Stucki M, Odate S, Puget N, et al. (2007) Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair. Mol Cell 28: 1045-1057. doi:10.1016/j.molcel.2007.12.005. PubMed: 18158901.
42. Jeggo PA, Löbrich M, (2007) DNA double-strand breaks: their cellular and clinical impact? Oncogene 26: 7717-7719. doi:10.1038/sj.onc.1210868. PubMed: 18066083.
43. Coster G, Goldberg M, (2010) The cellular response to DNA damage: A focus on MDC1 and its interacting proteins. Nucleus 1: 166-178. doi:10.4161/nucl.1.2.11176. PubMed: 21326949.
44. Durocher D, Jackson SP, (2002) The FHA domain. FEBS Lett 513: 58-66. doi:10.1016/S0014-5793(01)03294-X. PubMed: 11911881.
45. Yu X, Chini CC, He M, Mer G, Chen J, (2003) The BRCT domain is a phospho-protein binding domain. Science 302: 639-642. doi:10.1126/science.1088753. PubMed: 14576433.
46. Manke IA, Lowery DM, Nguyen A, Yaffe MB, (2003) BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302: 636-639. doi:10.1126/science.1088877. PubMed: 14576432.
47. Rodriguez M, Yu X, Chen J, Songyang Z, (2003) Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. J Biol Chem 278: 52914-52918. doi:10.1074/jbc.C300407200. PubMed: 14578343.
48. Linke SP, Sengupta S, Khabie N, Jeffries BA, Buchhop S, et al. (2003) p53 interacts with hRAD51 and hRAD54, and directly modulates homologous recombination. Cancer Res 63: 2596-2605. PubMed: 12750285.
49. Arias-Lopez C, Lazaro-Trueba I, Kerr P, Lord CJ, Dexter T, et al. (2006) p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene. EMBO Rep 7: 219-224. doi:10.1038/sj.embor.7400587. PubMed: 16322760.
50. Verma S, Rao BJ, (2013) p53 suppresses BRCA2-stimulated ATPase and strand exchange functions of human RAD51. J Biochem, 154: 237-48. PubMed: 23678008.
51. Lazaro-Trueba I, Arias C, Silva A, (2006) Double bolt regulation of Rad51 by p53: a role for transcriptional repression. Cell Cycle 5: 1062-1065. doi:10.4161/cc.5.10.2764. PubMed: 16721049.
52. Romanova LY, Willers H, Blagosklonny MV, Powell SN, (2004) The interaction of p53 with replication protein A mediates suppression of homologous recombination. Oncogene 23: 9025-9033. doi:10.1038/sj.onc.1207982. PubMed: 15489903.
53. Ozaki T, Nagase T, Ichimiya S, Seki N, Ohiri M, et al. (2000) NFBD1/KIAA0170 is a novel nuclear transcriptional transactivator with BRCT domain. DNA Cell Biol 19: 475-485. doi:10.1089/10445490050128403. PubMed: 10975465.
54. Nakanishi M, Ozaki T, Yamamoto H, Hanamoto T, Kikuchi H, et al. (2007) NFBD1/MDC1 associates with p53 and regulates its function at the crossroad between cell survival and death in response to DNA damage. J Biol Chem 282: 22993-23004. doi:10.1074/jbc.M611412200. PubMed: 17535811.
55. Efeyan A, Serrano M, (2007) p53: guardian of the genome and policeman of the oncogenes. Cell Cycle 6: 1006-1010. doi:10.4161/cc.6.9.4211. PubMed: 17457049.
56. Eliezer Y, Argaman L, Rhie A, Doherty AJ, Goldberg M, (2009) The direct interaction between 53BP1 and MDC1 is required for the recruitment of 53BP1 to sites of damage. J Biol Chem 284: 426-435. PubMed: 18986980.
57. Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S, (1994) Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci U S A 91: 6098-6102. doi:10.1073/pnas.91.13.6098. PubMed: 8016121.
58. Lou Z, Minter-Dykhouse K, Wu X, Chen J, (2003) MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Nature 421: 957-961. doi:10.1038/nature01447. PubMed: 12607004.
59. Kapoor M, Lozano G, (1998) Functional activation of p53 via phosphorylation following DNA damage by UV but not gamma radiation. Proc Natl Acad Sci U S A 95: 2834-2837. doi:10.1073/pnas.95.6.2834. PubMed: 9501176.
60. Saito S, Yamaguchi H, Higashimoto Y, Chao C, Xu Y, et al. (2003) Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J Biol Chem 278: 37536-37544. doi:10.1074/jbc.M305135200. PubMed: 12860987.
61. Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, et al. (2005) MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123: 1213-1226. doi:10.1016/j.cell.2005.09.038. PubMed: 16377563.
62. Bell S, Klein C, Müller L, Hansen S, Buchner J, (2002) p53 contains large unstructured regions in its native state. J Mol Biol 322: 917-927. doi:10.1016/S0022-2836(02)00848-3. PubMed: 12367518.
63. Stürzbecher HW, Brain R, Addison C, Rudge K, Remm M, et al. (1992) A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization. Oncogene 7: 1513-1523. PubMed: 1321401.
64. Jungmichel S, Stucki M, (2010) MDC1: The art of keeping things in focus. Chromosoma 119: 337-349. doi:10.1007/s00412-010-0266-9. PubMed: 20224865.
65. Iwabuchi K, Basu BP, Kysela B, Kurihara T, Shibata M, et al. (2003) Potential role for 53BP1 in DNA end-joining repair through direct interaction with DNA. J Biol Chem 278: 36487-36495. doi:10.1074/jbc.M304066200. PubMed: 12824158.
66. Poyurovsky MV, Katz C, Laptenko O, Beckerman R, Lokshin M, et al. (2010) The C terminus of p53 binds the N-terminal domain of MDM2. Nat Struct Mol Biol 17: 982-989. doi:10.1038/nsmb.1872. PubMed: 20639885.
67. 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. doi:10.1016/0092-8674(92)90644-R. PubMed: 1535557.
68. Oliner JD, (1993) Discerning the function of p53 by examining its molecular interactions. Bioessays 15: 703-707. doi:10.1002/bies.950151102. PubMed: 8292000.
69. Carter S, Bischof O, Dejean A, Vousden KH, (2007) C-terminal modifications regulate MDM2 dissociation and nuclear export of p53. Nat Cell Biol 9: 428-435. doi:10.1038/ncb1562. PubMed: 17369817.
70. Tang Y, Zhao W, Chen Y, Zhao Y, Gu W, (2008) Acetylation is indispensable for p53 activation. Cell 133: 612-626. doi:10.1016/j.cell.2008.03.025. PubMed: 18485870.
71. Mujtaba S, He Y, Zeng L, Yan S, Plotnikova O, et al. (2004) Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mol Cell 13: 251-263. doi:10.1016/S1097-2765(03)00528-8. PubMed: 14759370.
72. Horikoshi N, Usheva A, Chen J, Levine AJ, Weinmann R, et al. (1995) Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression. Mol Cell Biol 15: 227-234. PubMed: 7799929.
73. Gabizon R, Brandt T, Sukenik S, Lahav N, Lebendiker M, et al. (2012) Specific recognition of p53 tetramers by peptides derived from p53 interacting proteins. PLOS ONE 7: e38060. doi:10.1371/journal.pone.0038060. PubMed: 22693587.
74. Weber PJ, Bader JE, Folkers G, Beck-Sickinger AG, (1998) A fast and inexpensive method for N-terminal fluorescein-labeling of peptides. Bioorg Med Chem Lett 8: 597-600. doi:10.1016/S0960-894X(98)00084-5. PubMed: 9871567.
75. Li J, Williams BL, Haire LF, Goldberg M, Wilker E, et al. (2002) Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2. Mol Cell 9: 1045-1054. doi:10.1016/S1097-2765(02)00527-0. PubMed: 12049740.
76. Berendsen H, Postma J, van Gunsteren W, Hermans J, Pullman B, (1981) Intermolecular forces: Interaction models for water in relation to protein hydration. Dordrecht: Reidel. pp. pp. 331-342.
77. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, et al. (2005) GROMACS: fast, flexible, and free. J Comput Chem 26: 1701-1718. doi:10.1002/jcc.20291. PubMed: 16211538.
78. Berendsen HJC, van der Spoel D, van Drunen R, (1995) GROMACS- a message- passing parallel molecular-dynamics implementation. Comp Phys Comm 91: 43-56.
79. Siu SW, Vácha R, Jungwirth P, Böckmann RA, (2008) Biomolecular simulations of membranes: physical properties from different force fields. J Chem Phys 128: 125103. doi:10.1063/1.2897760. PubMed: 18376978.
80. Allen WJ, Capelluto DG, Finkielstein CV, Bevan DR, (2010) Modeling the relationship between the p53 C-terminal domain and its binding partners using molecular dynamics. J Phys Chem B 114: 13201-13213. doi:10.1021/jp1011445. PubMed: 20873738.
81. Hess B, Berendsen H, Fraaije J, (1997) LINCS: A linear constraint solver for molecular simulations. J Comput Chem 18: 1463-1472. doi:10.1002/(SICI)1096-987X(199709)18:12.
82. Parrinello M, Rahman A, (1981) Polymorphic Transitions in Single Crystals: A New Molecular Dynamics Method. J Appl Phys 52: 7182-7190. doi:10.1063/1.328693.
83. Darden T, York D, Pedersen L, (1993) Particle mesh Ewald: an N-log(N) method for Ewald sums in large systems. J Chem Phys 98: 10089-10092. doi:10.1063/1.464397.