Regulation of p53 DNA Binding

  • Kristine McKinney
  • Carol Prives
Chapter

p53 is one of the most frequently mutated genes in human cancers and, as a result, is also one of the most well-studied genes in the history of cancer research. Although many functions have been ascribed to p53 over the years, one of the first activities to be characterized was the ability to bind DNA sequence-specifically through its central domain (reviewed in Vogelstein & Kinzler, 1992). This domain, also frequently referred to as “the core” due to its protease resistance (Bargonetti et al., 1993; Pavletich et al., 1993), contains the most evolutionarily conserved sequences of the protein, both between p53 proteins from different species and between the different p53 family members, p63 and p73 (reviewed in Yang et al., 2002). This region is also the most frequently mutated domain of p53 in the major forms of human cancer (Hainaut & Hollstein, 2000; Olivier et al., 2002). Consequently much research has focused on understanding this crucial ability as well as its regulation. Indeed, the regulation of p53 DNA binding has generated much debate recently, specifically with regard to the role of the C-terminus.

Keywords

Core Domain Tetramerization Domain 
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References

  1. Abarzua P., LoSardo J. E., Gubler M. L., Neri A. Microinjection of monoclonal antibody PAb421 into human SW480 colorectal carcinoma cells restores the transcription activation function to mutant p53. Cancer Res 1995; 55:3490-4.PubMedGoogle Scholar
  2. Abarzua P., LoSardo J. E., Gubler M. L., Spathis R., Lu Y. A., Felix A., Neri A. Restoration of the transcription activation function to mutant p53 in human cancer cells. Oncogene 1996; 13:2477-82.PubMedGoogle Scholar
  3. Ahn J., Prives C. The C-terminus of p53: the more you learn the less you know. Nat Struct Biol 2001; 8:730-2.PubMedGoogle Scholar
  4. An W., Kim J., Roeder R. G. Ordered Cooperative Functions of PRMT1, p300, and CARM1 in Transcriptional Activation by p53. Cell 2004; 117:735-48.PubMedGoogle Scholar
  5. Anderson M. E., Woelker B., Reed M., Wang P., Tegtmeyer P. Reciprocal interference between the sequence-specific core and nonspecific C-terminal DNA binding domains of p53: implications for regulation. Mol Cell Biol 1997; 17:6255-64.PubMedGoogle Scholar
  6. Appella E., Anderson C. W. Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 2001; 268:2764-72.PubMedGoogle Scholar
  7. Avantaggiati M. L., Ogryzko V., Gardner K., Giordano A., Levine A. S., Kelly K. Recruitment of p300/CBP in p53-dependent signal pathways. Cell 1997; 89:1175-84.PubMedGoogle Scholar
  8. Ayed A., Mulder F. A., Yi G. S., Lu Y., Kay L. E., Arrowsmith C. H. Latent and active p53 are identical in conformation. Nat Struct Biol 2001; 8:756-60.PubMedGoogle Scholar
  9. Bakalkin G., Selivanova G., Yakovleva T., Kiseleva E., Kashuba E., Magnusson K. P., Szekely L., Klein G., Terenius L., Wiman K. G. p53 binds single-stranded DNA ends through the C-terminal domain and internal DNA segments via the middle domain. Nucleic Acids Res 1995; 23:362-9.PubMedGoogle Scholar
  10. Bakalkin G., Yakovleva T., Selivanova G., Magnusson K. P., Szekely L., Kiseleva E., Klein G., Terenius L., Wiman K. G. p53 binds single-stranded DNA ends and catalyzes DNA renaturation and strand transfer. Proc Natl Acad Sci U S A 1994; 91:413-7.PubMedGoogle Scholar
  11. Balagurumoorthy P., Sakamoto H., Lewis M. S., Zambrano N., Clore G. M., Gronenborn A. M., Appella E., Harrington R. E. Four p53 DNA-binding domain peptides bind natural p53-response elements and bend the DNA. Proc Natl Acad Sci U S A 1995; 92:8591-5.PubMedGoogle Scholar
  12. Baptiste N., Friedlander P., Chen X., Prives C. The proline-rich domain of p53 is required for cooperation with anti-neoplastic agents to promote apoptosis of tumor cells. Oncogene 2002; 21:9-21.PubMedGoogle Scholar
  13. Baptiste N., Prives C. p53 in the cytoplasm: a question of overkill? Cell 2004; 116:487-9.PubMedGoogle Scholar
  14. Bargonetti J., Manfredi J. J., Chen X., Marshak D. R., Prives C. A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. Genes Dev 1993; 7:2565-74.PubMedGoogle Scholar
  15. Barlev N. A., Liu L., Chehab N. H., Mansfield K., Harris K. G., Halazonetis T. D., Berger S.L. Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 2001; 8:1243-54.PubMedGoogle Scholar
  16. Boyd S. D., Tsai K. Y., Jacks T. An intact HDM2 RING-finger domain is required for nuclear exclusion of p53. Nat Cell Biol 2000; 2:563-8.PubMedGoogle Scholar
  17. Budhram-Mahadeo V., Morris P. J., Smith M. D., Midgley C. A., Boxer L. M., Latchman D. S. p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor. J Biol Chem 1999; 274:15237-44.PubMedGoogle Scholar
  18. Bullock A. N., Fersht A. R. Rescuing the function of mutant p53. Nat Rev Cancer 2001; 1:68-76.PubMedGoogle Scholar
  19. Buzek J., Latonen L., Kurki S., Peltonen K., Laiho M. Redox state of tumor suppressor p53 regulates its sequence-specific DNA binding in DNA-damaged cells by cysteine 277. Nucleic Acids Res 2002; 30:2340-8.PubMedGoogle Scholar
  20. Bykov V. J., Issaeva N., Shilov A., Hultcrantz M., Pugacheva E., Chumakov P., Bergman J., Wiman K. G., Selivanova G. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 2002; 8:282-8.PubMedGoogle Scholar
  21. Cain C., Miller S., Ahn J., Prives C. The N terminus of p53 regulates its dissociation from DNA. J Biol Chem 2000; 275:39944-53.PubMedGoogle Scholar
  22. Candau R., Scolnick D. M., Darpino P., Ying C. Y., Halazonetis T. D., Berger S. L. Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity. Oncogene 1997; 15:807-16.PubMedGoogle Scholar
  23. Cawley S., Bekiranov S., Ng H. H., Kapranov P., Sekinger E. A., Kampa D., Piccolboni A., Sementchenko V., Cheng J., Williams A. J., Wheeler R., Wong B., Drenkow J., Yamanaka M., Patel S., Brubaker S., Tammana H., Helt G., Struhl K., Gingeras T. R. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 2004; 116:499-509.PubMedGoogle Scholar
  24. Chang J., Kim D. H., Lee S. W., Choi K. Y., Sung Y. C. Transactivation ability of p53 transcriptional activation domain is directly related to the binding affinity to TATA-binding protein. J Biol Chem 1995; 270:25014-9.PubMedGoogle Scholar
  25. Chao C., Hergenhahn M., Kaeser M. D., Wu Z., Saito S., Iggo R., Hollstein M., Appella E., Xu Y. Cell type- and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses. J Biol Chem 2003.Google Scholar
  26. Chen X., Ko L. J., Jayaraman L., Prives C. p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 1996; 10:2438-51.PubMedGoogle Scholar
  27. Chene P. The role of tetramerization in p53 function. Oncogene 2001; 20:2611-7.PubMedGoogle Scholar
  28. Cherny D. I., Striker G., Subramaniam V., Jett S. D., Palecek E., Jovin T. M. DNA bending due to specific p53 and p53 core domain-DNA interactions visualized by electron microscopy. J Mol Biol 1999; 294:1015-26.PubMedGoogle Scholar
  29. Chipuk J. E., Green D. R. Cytoplasmic p53: Bax and Forward. Cell Cycle 2004; 3:429-31.PubMedGoogle Scholar
  30. Chipuk J. E., Kuwana T., Bouchier-Hayes L., Droin N. M., Newmeyer D. D., Schuler M., Green D. R. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 2004; 303:1010-4.PubMedGoogle Scholar
  31. Chipuk J. E., Maurer U., Green D. R., Schuler M. Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell 2003; 4:371-81.PubMedGoogle Scholar
  32. Cho Y., Gorina S., Jeffrey P. D., Pavletich N. P. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 1994; 265:346-55.PubMedGoogle Scholar
  33. Contente A., Dittmer A., Koch M. C., Roth J., Dobbelstein M. A polymorphic microsatellite that mediates induction of PIG3 by p53. Nat Genet 2002; 30:315-20.PubMedGoogle Scholar
  34. Dang C. V., Lee W. M. Nuclear and nucleolar targeting sequences of c-erb-A, c-myb, N-myc, p53, HSP70, and HIV tat proteins. J Biol Chem 1989; 264:18019-23.PubMedGoogle Scholar
  35. Di Como C. J., Gaiddon C., Prives C. p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol Cell Biol 1999; 19:1438-49.PubMedGoogle Scholar
  36. Di Como C. J., Prives C. Human tumor-derived p53 proteins exhibit binding site selectivity and temperature sensitivity for transactivation in a yeast-based assay. Oncogene 1998; 16:2527-39.PubMedGoogle Scholar
  37. Di Como C. J., Urist M. J., Babayan I., Drobnjak M., Hedvat C. V., Teruya-Feldstein J., Pohar K., Hoos A., Cordon-Cardo C. p63 expression profiles in human normal and tumor tissues. Clin Cancer Res 2002; 8:494-501.PubMedGoogle Scholar
  38. Dornan D., Shimizu H., Perkins N. D., Hupp T. R. DNA-dependent acetylation of p53 by the transcription coactivator p300. J Biol Chem 2003; 278:13431-41.PubMedGoogle Scholar
  39. Dudenhoffer C., Rohaly G., Will K., Deppert W., Wiesmuller L. Specific mismatch recognition in heteroduplex intermediates by p53 suggests a role in fidelity control of homologous recombination. Mol Cell Biol 1998; 18:5332-42.PubMedGoogle Scholar
  40. Dumont P., Leu J. I., Della Pietra A. C., 3rd, George D. L., Murphy M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 2003; 33:357-65.PubMedGoogle Scholar
  41. Espinosa J. M., Emerson B. M. Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment. Mol Cell 2001; 8:57-69.PubMedGoogle Scholar
  42. Espinosa J. M., Verdun R. E., Emerson B. M. p53 functions through stress- and promoter-specific recruitment of transcription initiation components before and after DNA damage. Mol Cell 2003; 12:1015-27.PubMedGoogle Scholar
  43. Flores E. R., Tsai K. Y., Crowley D., Sengupta S., Yang A., McKeon F., Jacks T. p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 2002; 416:560-4.PubMedGoogle Scholar
  44. Fojta M., Kubicarova T., Vojtesek B., Palecek E. Effect of p53 protein redox states on binding to supercoiled and linear DNA. J Biol Chem 1999; 274:25749-55.PubMedGoogle Scholar
  45. Foord O. S., Bhattacharya P., Reich Z., Rotter V. A DNA binding domain is contained in the C-terminus of wild type p53 protein. Nucleic Acids Res 1991; 19:5191-8.PubMedGoogle Scholar
  46. Foster B. A., Coffey H. A., Morin M. J., Rastinejad F. Pharmacological rescue of mutant p53 conformation and function. Science 1999; 286:2507-10.PubMedGoogle Scholar
  47. Friedlander P., Haupt Y., Prives C., Oren M. A mutant p53 that discriminates between p53-responsive genes cannot induce apoptosis. Mol Cell Biol 1996a; 16:4961-71.PubMedGoogle Scholar
  48. Friedlander P., Legros Y., Soussi T., Prives C. Regulation of mutant p53 temperature-sensitive DNA binding. J Biol Chem 1996b; 271:25468-78.PubMedGoogle Scholar
  49. Friedler A., Hansson L. O., Veprintsev D. B., Freund S. M., Rippin T. M., Nikolova P. V., Proctor M. R., Rudiger S., Fersht A. R. A peptide that binds and stabilizes p53 core domain: chaperone strategy for rescue of oncogenic mutants. Proc Natl Acad Sci U S A 2002; 99:937-42.PubMedGoogle Scholar
  50. Friedler A., Veprintsev D. B., Hansson L. O., Fersht A. R. Kinetic instability of p53 core domain mutants: implications for rescue by small molecules. J Biol Chem 2003; 278:24108-12.PubMedGoogle Scholar
  51. Gaiddon C., Lokshin M., Ahn J., Zhang T., Prives C. A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain. Mol Cell Biol 2001; 21:1874-87.PubMedGoogle Scholar
  52. Gaiddon C., Moorthy N. C., Prives C. Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. Embo J 1999; 18:5609-21.PubMedGoogle Scholar
  53. Geyer R. K., Yu Z. K., Maki C. G. The MDM2 RING-finger domain is required to promote p53 nuclear export. Nat Cell Biol 2000; 2:569-73.PubMedGoogle Scholar
  54. Gohler T., Reimann M., Cherny D., Walter K., Warnecke G., Kim E., Deppert W. Specific interaction of p53 with target binding sites is determined by DNA conformation and is regulated by the C-terminal domain. J Biol Chem 2002; 277:41192-203.PubMedGoogle Scholar
  55. Gorina S., Pavletich N. P. Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science 1996; 274:1001-5.PubMedGoogle Scholar
  56. Gostissa M., Hengstermann A., Fogal V., Sandy P., Schwarz S. E., Scheffner M., Del Sal G. Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. Embo J 1999; 18:6462-71.PubMedGoogle Scholar
  57. Gottifredi V., Karni-Schmidt O., Shieh S. S., Prives C. p53 down-regulates CHK1 through p21 and the retinoblastoma protein. Mol Cell Biol 2001; 21:1066-76.PubMedGoogle Scholar
  58. Green D. R., Evan G. I. A matter of life and death. Cancer Cell 2002; 1:19-30.PubMedGoogle Scholar
  59. Gu W., Roeder R. G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 1997; 90:595-606.PubMedGoogle Scholar
  60. Gu W., Shi X. L., Roeder R. G. Synergistic activation of transcription by CBP and p53. Nature 1997; 387:819-23.PubMedGoogle Scholar
  61. Hainaut P., Hollstein M. p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 2000; 77:81-137.PubMedGoogle Scholar
  62. Hainaut P., Mann K. Zinc binding and redox control of p53 structure and function. Antioxid Redox Signal 2001; 3:611-23.PubMedGoogle Scholar
  63. Hainaut P., Rolley N., Davies M., Milner J. Modulation by copper of p53 conformation and sequence-specific DNA binding: role for Cu(II)/Cu(I) redox mechanism. Oncogene 1995; 10:27-32.PubMedGoogle Scholar
  64. Halazonetis T. D., Davis L. J., Kandil A. N. Wild-type p53 adopts a 'mutant'-like conformation when bound to DNA. Embo J 1993; 12:1021-8.PubMedGoogle Scholar
  65. Halazonetis T. D., Kandil A. N. Conformational shifts propagate from the oligomerization domain of p53 to its tetrameric DNA binding domain and restore DNA binding to select p53 mutants. Embo J 1993; 12:5057-64.PubMedGoogle Scholar
  66. Hansen S., Hupp T. R., Lane D. P. Allosteric regulation of the thermostability and DNA binding activity of human p53 by specific interacting proteins. CRC Cell Transformation Group. J Biol Chem 1996; 271:3917-24.PubMedGoogle Scholar
  67. Harms K., Nozell S., Chen X. The common and distinct target genes of the p53 family transcription factors. Cell Mol Life Sci 2004; 61:822-42.PubMedGoogle Scholar
  68. Hoffman W. H., Biade S., Zilfou J. T., Chen J., Murphy M. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem 2002; 277:3247-57.PubMedGoogle Scholar
  69. Hoffmann R., Craik D. J., Pierens G., Bolger R. E., Otvos L., Jr. Phosphorylation of the C-terminal sites of human p53 reduces non-sequence-specific DNA binding as modeled with synthetic peptides. Biochemistry 1998; 37:13755-64.PubMedGoogle Scholar
  70. Hoh J., Jin S., Parrado T., Edington J., Levine A. J., Ott J. The p53MH algorithm and its application in detecting p53-responsive genes. Proc Natl Acad Sci U S A 2002; 99:8467-72.PubMedGoogle Scholar
  71. Hsu C. H., Chang M. D., Tai K. Y., Yang Y. T., Wang P. S., Chen C. J., Wang Y. H., Lee S.C., Wu C. W., Juan L. J. HCMV IE2-mediated inhibition of HAT activity downregulates p53 function. Embo J 2004; 23:2269-80.PubMedGoogle Scholar
  72. Hupp T. R., Lane D. P. Allosteric activation of latent p53 tetramers. Curr Biol 1994; 4:865-75.PubMedGoogle Scholar
  73. Hupp T. R., Meek D. W., Midgley C. A., Lane D. P. Regulation of the specific DNA binding function of p53. Cell 1992; 71:875-86.PubMedGoogle Scholar
  74. Hupp T. R., Sparks A., Lane D. P. Small peptides activate the latent sequence-specific DNA binding function of p53. Cell 1995; 83:237-45.PubMedGoogle Scholar
  75. Iwabuchi K., Bartel P. L., Li B., Marraccino R., Fields S. Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci U S A 1994; 91:6098-102.PubMedGoogle Scholar
  76. Jackson P., Mastrangelo I., Reed M., Tegtmeyer P., Yardley G., Barrett J. Synergistic transcriptional activation of the MCK promoter by p53: tetramers link separated DNA response elements by DNA looping. Oncogene 1998; 16:283-92.PubMedGoogle Scholar
  77. Jayaraman L., Prives C. Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus. Cell 1995; 81:1021-9.PubMedGoogle Scholar
  78. Jayaraman L., Moorthy N. C., Murthy K. G., Manley J. L., Bustin M., Prives C. High mobility group protein-1 (HMG-1) is a unique activator of p53. Genes Dev 1998; 12:462-72.PubMedGoogle Scholar
  79. Jayaraman L., Murthy K. G., Zhu C., Curran T., Xanthoudakis S., Prives C. Identification of redox/repair protein Ref-1 as a potent activator of p53. Genes Dev 1997; 11:558-70.PubMedGoogle Scholar
  80. Jayaraman L., Prives C. Covalent and noncovalent modifiers of the p53 protein. Cell Mol Life Sci 1999; 55:76-87.PubMedGoogle Scholar
  81. Jiang M., Axe T., Holgate R., Rubbi C. P., Okorokov A. L., Mee T., Milner J. p53 binds the nuclear matrix in normal cells: binding involves the proline-rich domain of p53 and increases following genotoxic stress. Oncogene 2001; 20:5449-58.Google Scholar
  82. Johnson R. A., Ince T. A., Scotto K. W. Transcriptional repression by p53 through direct binding to a novel DNA element. J Biol Chem 2001; 276:27716-20.PubMedGoogle Scholar
  83. Jost C. A., Marin M. C., Kaelin W. G., Jr. p73 is a simian [correction of human] p53-related protein that can induce apoptosis. Nature 1997; 389:191-4.PubMedGoogle Scholar
  84. Juan L. J., Shia W. J., Chen M. H., Yang W. M., Seto E., Lin Y. S., Wu C. W. Histone deacetylases specifically down-regulate p53-dependent gene activation. J Biol Chem 2000; 275:20436-43.PubMedGoogle Scholar
  85. Kaeser M. D., Iggo R. D. Chromatin immunoprecipitation analysis fails to support the latency model for regulation of p53 DNA binding activity in vivo. Proc Natl Acad Sci U S A 2002; 99:95-100.PubMedGoogle Scholar
  86. Kaeser M. D., Iggo R. D. Promoter-specific p53-dependent histone acetylation following DNA damage. Oncogene 2004; 23:4007-13.PubMedGoogle Scholar
  87. Kim A. L., Raffo A. J., Brandt-Rauf P. W., Pincus M. R., Monaco R., Abarzua P., Fine R. L. 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.PubMedGoogle Scholar
  88. Kim E., Albrechtsen N., Deppert W. DNA-conformation is an important determinant of sequence-specific DNA binding by tumor suppressor p53. Oncogene 1997; 15:857-69.PubMedGoogle Scholar
  89. Ko L. J., Prives C. p53: puzzle and paradigm. Genes Dev 1996; 10:1054-72.PubMedGoogle Scholar
  90. Kubbutat M. H., Ludwig R. L., Ashcroft M., Vousden K. H. Regulation of Mdm2-directed degradation by the C terminus of p53. Mol Cell Biol 1998; 18:5690-8.PubMedGoogle Scholar
  91. Lang F. F., Bruner J. M., Fuller G. N., Aldape K., Prados M. D., Chang S., Berger M. S., McDermott M. W., Kunwar S. M., Junck L. R., Chandler W., Zwiebel J. A., Kaplan R. S., Yung W. K. Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol 2003; 21:2508-18.PubMedGoogle Scholar
  92. Langley E., Pearson M., Faretta M., Bauer U. M., Frye R. A., Minucci S., Pelicci P. G., Kouzarides T. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. Embo J 2002; 21:2383-96.PubMedGoogle Scholar
  93. Lee K. C., Crowe A. J., Barton M. C. p53-mediated repression of alpha-fetoprotein gene expression by specific DNA binding. Mol Cell Biol 1999; 19:1279-88.PubMedGoogle Scholar
  94. Lee S., Cavallo L., Griffith J. Human p53 binds Holliday junctions strongly and facilitates their cleavage. J Biol Chem 1997; 272:7532-9.PubMedGoogle Scholar
  95. Lee S., Elenbaas B., Levine A., Griffith J. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell 1995; 81:1013-20.PubMedGoogle Scholar
  96. Lin J., Chen J., Elenbaas B., Levine A. J. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev 1994; 8:1235-46.PubMedGoogle Scholar
  97. Liu L., Scolnick D. M., Trievel R. C., Zhang H. B., Marmorstein R., Halazonetis T. D., Berger S. L. p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage. Mol Cell Biol 1999; 19:1202-9.PubMedGoogle Scholar
  98. Lohr K., Moritz C., Contente A., Dobbelstein M. p21/CDKN1A mediates negative regulation of transcription by p53. J Biol Chem 2003; 278:32507-16.PubMedGoogle Scholar
  99. Ludwig R. L., Bates S., Vousden K. H. Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function. Mol Cell Biol 1996; 16:4952-60.PubMedGoogle Scholar
  100. Luo J., Li M., Tang Y., Laszkowska M., Roeder R. G., Gu W. Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc Natl Acad Sci U S A 2004.Google Scholar
  101. Luo J., Nikolaev A. Y., Imai S., Chen D., Su F., Shiloh A., Guarente L., Gu W. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 2001; 107:137-48.Google Scholar
  102. Luo J., Su F., Chen D., Shiloh A., Gu W. Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 2000; 408:377-81.PubMedGoogle Scholar
  103. Manfredi J. J. p53 and apoptosis: it's not just in the nucleus anymore. Mol Cell 2003; 11:552-4.PubMedGoogle Scholar
  104. Mazur S. J., Sakaguchi K., Appella E., Wang X. W., Harris C. C., Bohr V. A. Preferential binding of tumor suppressor p53 to positively or negatively supercoiled DNA involves the C-terminal domain. J Mol Biol 1999; 292:241-9.PubMedGoogle Scholar
  105. McKinney K., Prives C. Efficient specific DNA binding by p53 requires both its central and C-terminal domains as revealed by studies with high-mobility group 1 protein. Mol Cell Biol 2002; 22:6797-808.PubMedGoogle Scholar
  106. McLure K. G., Lee P. W. How p53 binds DNA as a tetramer. Embo J 1998; 17:3342-50.PubMedGoogle Scholar
  107. Meplan C., Richard M. J., Hainaut P. Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells. Oncogene 2000; 19:5227-36.PubMedGoogle Scholar
  108. Michael D., Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol 2003; 13:49-58.PubMedGoogle Scholar
  109. Mihara M., Erster S., Zaika A., Petrenko O., Chittenden T., Pancoska P., Moll U. M. p53 has a direct apoptogenic role at the mitochondria. Mol Cell 2003; 11:577-90.PubMedGoogle Scholar
  110. Miyashita T., Reed J. C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 1995; 80:293-9.PubMedGoogle Scholar
  111. Mujtaba S., He Y., Zeng L., Yan S., Plotnikova O., Sachchidanand, Sanchez R., Zeleznik-Le N. J., Ronai Z., Zhou M. M. Structural Mechanism of the Bromodomain of the Coactivator CBP in p53 Transcriptional Activation. Mol Cell 2004; 13:251-63.Google Scholar
  112. Muller-Tiemann B. F., Halazonetis T. D., Elting J. J. Identification of an additional negative regulatory region for p53 sequence-specific DNA binding. Proc Natl Acad Sci U S A 1998; 95:6079-84.PubMedGoogle Scholar
  113. Nagaich A. K., Appella E., Harrington R. E. DNA bending is essential for the site-specific recognition of DNA response elements by the DNA binding domain of the tumor suppressor protein p53. J Biol Chem 1997a; 272:14842-9.PubMedGoogle Scholar
  114. Nagaich A. K., Zhurkin V. B., Durell S. R., Jernigan R. L., Appella E., Harrington R. E. p53-induced DNA bending and twisting: p53 tetramer binds on the outer side of a DNA loop and increases DNA twisting. Proc Natl Acad Sci U S A 1999; 96:1875-80.PubMedGoogle Scholar
  115. Nagaich A. K., Zhurkin V. B., Sakamoto H., Gorin A. A., Clore G. M., Gronenborn A. M., Appella E., Harrington R. E. Architectural accommodation in the complex of four p53 DNA binding domain peptides with the p21/waf1/cip1 DNA response element. J Biol Chem 1997b; 272:14830-41.PubMedGoogle Scholar
  116. Nie Y., Li H. H., Bula C. M., Liu X. Stimulation of p53 DNA binding by c-Abl requires the p53 C terminus and tetramerization. Mol Cell Biol 2000; 20:741-8.PubMedGoogle Scholar
  117. Nikolova P. V., Henckel J., Lane D. P., Fersht A. R. Semirational design of active tumor suppressor p53 DNA binding domain with enhanced stability. Proc Natl Acad Sci U S A 1998; 95:14675-80.PubMedGoogle Scholar
  118. Oda K., Arakawa H., Tanaka T., Matsuda K., Tanikawa C., Mori T., Nishimori H., Tamai K., Tokino T., Nakamura Y., Taya Y. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 2000; 102:849-62.PubMedGoogle Scholar
  119. Okorokov A. L., Rubbi C. P., Metcalfe S., Milner J. The interaction of p53 with the nuclear matrix is mediated by F-actin and modulated by DNA damage. Oncogene 2002; 21:356-67.PubMedGoogle Scholar
  120. Olivier M., Eeles R., Hollstein M., Khan M. A., Harris C. C., Hainaut P. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 2002; 19:607-14.PubMedGoogle Scholar
  121. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ 2003; 10:431-42.PubMedGoogle Scholar
  122. Ori A., Zauberman A., Doitsh G., Paran N., Oren M., Shaul Y. p53 binds and represses the HBV enhancer: an adjacent enhancer element can reverse the transcription effect of p53. Embo J 1998; 17:544-53.PubMedGoogle Scholar
  123. Pagliaro L. C., Keyhani A., Williams D., Woods D., Liu B., Perrotte P., Slaton J. W., Merritt J. A., Grossman H. B., Dinney C. P. Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer: a phase I study of p53 gene therapy. J Clin Oncol 2003; 21:2247-53.PubMedGoogle Scholar
  124. Palecek E., Brazda V., Jagelska E., Pecinka P., Karlovska L., Brazdova M. Enhancement of p53 sequence-specific binding by DNA supercoiling. Oncogene 2004.Google Scholar
  125. Parks D., Bolinger R., Mann K. Redox state regulates binding of p53 to sequence-specific DNA, but not to non-specific or mismatched DNA. Nucleic Acids Res 1997; 25:1289-95.PubMedGoogle Scholar
  126. Pavletich N. P., Chambers K. A., Pabo C. O. The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev 1993; 7:2556-64.PubMedGoogle Scholar
  127. Rainwater R., Parks D., Anderson M. E., Tegtmeyer P., Mann K. Role of cysteine residues in regulation of p53 function. Mol Cell Biol 1995; 15:3892-903.PubMedGoogle Scholar
  128. Reed M., Woelker B., Wang P., Wang Y., Anderson M. E., Tegtmeyer P. The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation. Proc Natl Acad Sci U S A 1995; 92:9455-9.PubMedGoogle Scholar
  129. Resnick M. A., Inga A. Functional mutants of the sequence-specific transcription factor p53 and implications for master genes of diversity. Proc Natl Acad Sci U S A 2003; 100:9934-9.PubMedGoogle Scholar
  130. Resnick-Silverman L., St Clair S., Maurer M., Zhao K., Manfredi J. J. Identification of a novel class of genomic DNA-binding sites suggests a mechanism for selectivity in target gene activation by the tumor suppressor protein p53. Genes Dev 1998; 12:2102-7.PubMedGoogle Scholar
  131. Rippin T. M., Freund S. M., Veprintsev D. B., Fersht A. R. Recognition of DNA by p53 core domain and location of intermolecular contacts of cooperative binding. J Mol Biol 2002; 319:351-8.PubMedGoogle Scholar
  132. Rodriguez M. S., Desterro J. M., Lain S., Lane D. P., Hay R. T. Multiple C-terminal lysine residues target p53 for ubiquitin-proteasome-mediated degradation. Mol Cell Biol 2000; 20:8458-67.PubMedGoogle Scholar
  133. Rodriguez M. S., Desterro J. M., Lain S., Midgley C. A., Lane D. P., Hay R. T. SUMO-1 modification activates the transcriptional response of p53. Embo J 1999; 18:6455-61.PubMedGoogle Scholar
  134. Sakaguchi K., Herrera J. E., Saito S., Miki T., Bustin M., Vassilev A., Anderson C. W., Appella E. DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev 1998; 12:2831-41.PubMedGoogle Scholar
  135. Sakamuro D., Sabbatini P., White E., Prendergast G. C. The polyproline region of p53 is required to activate apoptosis but not growth arrest. Oncogene 1997; 15:887-98.PubMedGoogle Scholar
  136. Saller E., Tom E., Brunori M., Otter M., Estreicher A., Mack D. H., Iggo R. Increased apoptosis induction by 121F mutant p53. Embo J 1999; 18:4424-37.PubMedGoogle Scholar
  137. Samuels-Lev Y., O'Connor D. J., Bergamaschi D., Trigiante G., Hsieh J. K., Zhong S., Campargue I., Naumovski L., Crook T., Lu X. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell 2001; 8:781-94.PubMedGoogle Scholar
  138. Scolnick D. M., Chehab N. H., Stavridi E. S., Lien M. C., Caruso L., Moran E., Berger S. L., Halazonetis T. D. CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein. Cancer Res 1997; 57:3693-6.PubMedGoogle Scholar
  139. Selivanova G., Iotsova V., Okan I., Fritsche M., Strom M., Groner B., Grafstrom R. C., Wiman K. G. 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.PubMedGoogle Scholar
  140. Seo Y. R., Kelley M. R., Smith M. L. Selenomethionine regulation of p53 by a ref1-dependent redox mechanism. Proc Natl Acad Sci U S A 2002; 99:14548-53.PubMedGoogle Scholar
  141. Shaulsky G., Goldfinger N., Ben-Ze'ev A., Rotter V. Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. Mol Cell Biol 1990; 10:6565-77.PubMedGoogle Scholar
  142. Stenger J. E., Tegtmeyer P., Mayr G. A., Reed M., Wang Y., Wang P., Hough P. V., Mastrangelo I. A. p53 oligomerization and DNA looping are linked with transcriptional activation. Embo J 1994; 13:6011-20.PubMedGoogle Scholar
  143. Stommel J. M., Marchenko N. D., Jimenez G. S., Moll U. M., Hope T. J., Wahl G. M. 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.PubMedGoogle Scholar
  144. Strano S., Fontemaggi G., Costanzo A., Rizzo M. G., Monti O., Baccarini A., Del Sal G., Levrero M., Sacchi A., Oren M., Blandino G. Physical interaction with human tumor-derived p53 mutants inhibits p63 activities. J Biol Chem 2002; 277:18817-26.PubMedGoogle Scholar
  145. Strano S., Munarriz E., Rossi M., Cristofanelli B., Shaul Y., Castagnoli L., Levine A. J., Sacchi A., Cesareni G., Oren M., Blandino G. Physical and functional interaction between p53 mutants and different isoforms of p73. J Biol Chem 2000; 275:29503-12.PubMedGoogle Scholar
  146. Stros M., Muselikova-Polanska E., Pospisilova S., Strauss F. High-Affinity Binding of Tumor-Suppressor Protein p53 and HMGB1 to Hemicatenated DNA Loops. Biochemistry 2004; 43:7215-25.PubMedGoogle Scholar
  147. Takenaka I., Morin F., Seizinger B. R., Kley N. Regulation of the sequence-specific DNA binding function of p53 by protein kinase C and protein phosphatases. J Biol Chem 1995; 270:5405-11.PubMedGoogle Scholar
  148. Thornborrow E. C., Manfredi J. J. One mechanism for cell type-specific regulation of the bax promoter by the tumor suppressor p53 is dictated by the p53 response element. J Biol Chem 1999; 274:33747-56.PubMedGoogle Scholar
  149. Ueno M., Masutani H., Arai R. J., Yamauchi A., Hirota K., Sakai T., Inamoto T., Yamaoka Y., Yodoi J., Nikaido T. Thioredoxin-dependent redox regulation of p53-mediated p21 activation. J Biol Chem 1999; 274:35809-15.PubMedGoogle Scholar
  150. Unger T., Mietz J. A., Scheffner M., Yee C. L., Howley P. M. Functional domains of wild-type and mutant p53 proteins involved in transcriptional regulation, transdominant inhibition, and transformation suppression. Mol Cell Biol 1993; 13:5186-94.PubMedGoogle Scholar
  151. Urist M. J., Di Como C. J., Lu M. L., Charytonowicz E., Verbel D., Crum C. P., Ince T. A., McKeon F. D., Cordon-Cardo C. Loss of p63 expression is associated with tumor progression in bladder cancer. Am J Pathol 2002; 161:1199-206.PubMedGoogle Scholar
  152. Vaziri H., Dessain S. K., Ng Eaton E., Imai S. I., Frye R. A., Pandita T. K., Guarente L., Weinberg R. A. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001; 107:149-59.PubMedGoogle Scholar
  153. Venot C., Maratrat M., Dureuil C., Conseiller E., Bracco L., Debussche L. The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific PIG3 gene transactivation and with transcriptional repression. Embo J 1998; 17:4668-79.PubMedGoogle Scholar
  154. Venot C., Maratrat M., Sierra V., Conseiller E., Debussche L. Definition of a p53 transactivation function-deficient mutant and characterization of two independent p53 transactivation subdomains. Oncogene 1999; 18:2405-10.PubMedGoogle Scholar
  155. Verhaegh G. W., Richard M. J., Hainaut P. Regulation of p53 by metal ions and by antioxidants: dithiocarbamate down-regulates p53 DNA-binding activity by increasing the intracellular level of copper. Mol Cell Biol 1997; 17:5699-706.PubMedGoogle Scholar
  156. Vogelstein B., Kinzler K. W. p53 function and dysfunction. Cell 1992; 70:523-6.PubMedGoogle Scholar
  157. Walker K. K., Levine A. J. Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Acad Sci U S A 1996; 93:15335-40.PubMedGoogle Scholar
  158. Wang W., Takimoto R., Rastinejad F., El-Deiry W. S. Stabilization of p53 by CP-31398 inhibits ubiquitination without altering phosphorylation at serine 15 or 20 or MDM2 binding. Mol Cell Biol 2003; 23:2171-81.PubMedGoogle Scholar
  159. Wang Y., Reed M., Wang P., Stenger J. E., Mayr G., Anderson M. E., Schwedes J. F., Tegtmeyer P. p53 domains: identification and characterization of two autonomous DNA-binding regions. Genes Dev 1993; 7:2575-86.PubMedGoogle Scholar
  160. Waterman M. J., Stavridi E. S., Waterman J. L., Halazonetis T. D. ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat Genet 1998; 19:175-8.PubMedGoogle Scholar
  161. Waterman M. J., Waterman J. L., Halazonetis T. D. An engineered four-stranded coiled coil substitutes for the tetramerization domain of wild-type p53 and alleviates transdominant inhibition by tumor-derived p53 mutants. Cancer Res 1996; 56:158-63.PubMedGoogle Scholar
  162. Wieczorek A. M., Waterman J. L., Waterman M. J., Halazonetis T. D. Structure-based rescue of common tumor-derived p53 mutants. Nat Med 1996; 2:1143-6.PubMedGoogle Scholar
  163. Willis A., Jung E. J., Wakefield T., Chen X. Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes. Oncogene 2004. Wilson D. R. Viral-mediated gene transfer for cancer treatment. Curr Pharm Biotechnol 2002; 3:151-64.Google Scholar
  164. Wong K. B., DeDecker B. S., Freund S. M., Proctor M. R., Bycroft M., Fersht A. R. Hot-spot mutants of p53 core domain evince characteristic local structural changes. Proc Natl Acad Sci U S A 1999; 96:8438-42.PubMedGoogle Scholar
  165. Wu L., Bayle J. H., Elenbaas B., Pavletich N. P., Levine A. J. Alternatively spliced forms in the carboxy-terminal domain of the p53 protein regulate its ability to promote annealing of complementary single strands of nucleic acids. Mol Cell Biol 1995; 15:497-504.PubMedGoogle Scholar
  166. Yakovleva T., Pramanik A., Kawasaki T., Tan-No K., Gileva I., Lindegren H., Langel U., Ekstrom T. J., Rigler R., Terenius L., Bakalkin G. p53 Latency. C-terminal domain prevents binding of p53 core to target but not to nonspecific DNA sequences. J Biol Chem 2001; 276:15650-8.PubMedGoogle Scholar
  167. Yang A., Kaghad M., Caput D., McKeon F. On the shoulders of giants: p63, p73 and the rise of p53. Trends Genet 2002; 18:90-5.PubMedGoogle Scholar
  168. Yang A., Kaghad M., Wang Y., Gillett E., Fleming M. D., Dotsch V., Andrews N. C., Caput D., McKeon F. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 1998; 2:305-16.PubMedGoogle Scholar
  169. Yew P. R., Liu X., Berk A. J. Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev 1994; 8:190-202.PubMedGoogle Scholar
  170. Zhou J., Prives C. Replication of damaged DNA in vitro is blocked by p53. Nucleic Acids Res 2003; 31:3881-92.PubMedGoogle Scholar
  171. Zhu J., Jiang J., Zhou W., Zhu K., Chen X. Differential regulation of cellular target genes by p53 devoid of the PXXP motifs with impaired apoptotic activity. Oncogene 1999; 18:2149-55.PubMedGoogle Scholar
  172. Zhu J., Zhang S., Jiang J., Chen X. Definition of the p53 functional domains necessary for inducing apoptosis. J Biol Chem 2000; 275:39927-34.PubMedGoogle Scholar
  173. Zhu J., Zhou W., Jiang J., Chen X. Identification of a novel p53 functional domain that is necessary for mediating apoptosis. J Biol Chem 1998; 273:13030-6.PubMedGoogle Scholar
  174. Zilfou J. T., Hoffman W. H., Sank M., George D. L., Murphy M. The corepressor mSin3a interacts with the proline-rich domain of p53 and protects p53 from proteasome-mediated degradation. Mol Cell Biol 2001; 21:3974-85.PubMedGoogle Scholar
  175. Zotchev S. B., Protopopova M., Selivanova G. p53 C-terminal interaction with DNA ends and gaps has opposing effect on specific DNA binding by the core. Nucleic Acids Res 2000; 28:4005-12.PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Kristine McKinney
    • 1
  • Carol Prives
    • 1
  1. 1.Department of Biological SciencesColumbia UniversityNew YorkUSA

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