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Apoptosis, cancer and the p53 tumour suppressor gene

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Abstract

One of the most commonly detected abnormalities in human cancer is mutation of the p53 tumour suppressor gene. Intrinsic to the function of p53 is its ability to induce apoptotic cell death and to cause cell cycle arrest. Moreover, p53 plays an important role in controlling the cellular response to DNA damaging agents such as ionizing radiation and cancer chemotherapeutic drugs. Loss of p53 function causes increased resistance to radiation and chemotherapeutic agents, and there is increasing evidence that p53 mutational status is an important determinant of clinical outcome in cancer. This review will focus on recent data describing the biochemistry of p53 function, its role in mediating apoptosis and cell cycle arrest and in the control of tumour growth and death.

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References

  1. Levine AJ: The tumor suppressor genes. Ann Rev Biochem 62: 623–651, 1993

    Google Scholar 

  2. Soussi T, de Fromentel CC, May P: Structural aspects of the p53 protein in relation to gene evolution. Oncogene 5: 945–952, 1990

    Google Scholar 

  3. Linzer DIH, Levine AJ: Characterization of a 54 K dalton cellular SV40 tumour antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17: 43–52, 1979

    Google Scholar 

  4. Lane DP, Crawford LV: T antigen is bound to a host protein in SV40-transformed cells. Nature 278: 261–263, 1979

    Google Scholar 

  5. Mowat MA, Cheng A, Kimura N, Bernstein A, Benchimol S: Rearrangements of the cellular p53 gene in erythroleukemic cells transformed by Friend virus. Nature 314: 633–636, 1985

    Google Scholar 

  6. Baker SJ, Markowitz S, Fearon ER, Wilson JKV, Vogelstein B: Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 244: 217–222, 1989

    Google Scholar 

  7. Finlay CA, Hinds PW, Levine AJ: The p53 proto-oncogene can act as a suppressor of transformation. Cell 57: 1083–1093, 1989

    Google Scholar 

  8. Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O, Oren M: Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci (USA) 86: 8763–8767, 1989

    Google Scholar 

  9. Michalovitz D, Halevy O, Oren M: Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. Cell 62: 671–680, 1990

    Google Scholar 

  10. Baker SJ, Markowitz S, Fearon ER, Wilson JKV, Vogelstein B: Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249: 912–915, 1990

    Google Scholar 

  11. Chen P-L, Chen Y, Bookstein R, Lee W-H: Genetic mechanisms of tumor suppression by the human p53 gene. Science 250: 1576–1580, 1990

    Google Scholar 

  12. Martinez J, Geogoff I, Marinez J, Levine AJ: Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes Dev 5: 151–159, 1991

    Google Scholar 

  13. Harris CC: p53: At the crossroads of molecular carcinogenesis and risk assessment. Science 262: 1980–1981, 1993

    Google Scholar 

  14. Hollstein M, Sidransky D, Vogelstein B, Harris C: p53 mutations in human cancer. Science 49: 49–53, 1991

    Google Scholar 

  15. Greenblatt MS, Bennett WP, Hollstein M, Harris CC: Mutations in the p53 tumour suppressor gene: Clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855–4878, 1994

    Google Scholar 

  16. Jenkins JR, Rudge K, Currie GA: Cellular immortalization by a cDNA clone encoding the transformation associated phosphoprotein p53. Nature 312: 651–654, 1984

    Google Scholar 

  17. Eliyahu D, Raz A, Gruss P, Givol D, Oren M: Participation of the p53 cellular tumour antigen in transformation of normal embryonic cells. Nature 312: 646–648, 1984

    Google Scholar 

  18. Parada LF, Land H, Weinberg RA, Wolf D, Rotter V: Cooperation between the gene encoding the p53 tumour antigen andras in cellular transformation. Nature 312: 649–651, 1984

    Google Scholar 

  19. Bargonetti J, Friedman PN, Kern SK, Vogelstein B, Prives C: Wild-type p53 but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication. Cell 65: 1083–1091, 1991

    Google Scholar 

  20. Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C, Vogelstein B: Identification of p53 as a sequencespecific DNA-binding protein. Science 252: 1708–1711, 1991

    Google Scholar 

  21. McCormick F, Clark FR, Harlow E, Tijan R: SV40 T antigen binds specifically to a cellular 53K proteinin vitro. Nature 292: 63–65, 1981

    Google Scholar 

  22. Schmieg FI, Simmons DT: Characterization of thein vitro interaction between SV40 T antigen and p53: Mapping the p53 binding site. Virology 164: 132–140, 1988

    Google Scholar 

  23. Agoff SN, Hou J, Linzer DIH, Wu B: Regulation of the human hsp70 promoter by p53. Science 259: 84–87, 1993

    Google Scholar 

  24. Seto E, Usheva A, Zambetti GP, Momand J, Horikoshi N, Weinmann R, Levine AJ, Shenk T: Wild-type p53 binds to the TATA-binding protein and represses transcription. Proc Natl Acad Sci (USA) 89: 12028–12032, 1992

    Google Scholar 

  25. Truant R, Xia H, Ingles CJ, Greenblatt J: Direct interaction between the transcriptional activation domain of human p53 and the TATA box-binding protein. J Biol Chem 268: 2284–2287, 1993

    Google Scholar 

  26. Unger T, Nau MM, Segal S, Minna JD: p53: a transdominant regulator of transcription whose function is ablated by mutations occurring in human cancer, EMBO J 11: 1383–1390, 1992

    Google Scholar 

  27. Pavletich NP, Chambers KA, Pabo CO: The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev 7: 2556–2564, 1993

    Google Scholar 

  28. Bargonetti J, Manfredi JJ, Chen X, Marshak DR, 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 7: 2565–2574, 1993

    Google Scholar 

  29. Sturzbecher H-W, Brain R, Addison C, Rudge K, Remm M, Grimaldi M, Keenan E, Jenkins JR: A C-terminal α-helix plus basic region motif is the major structural determinant of p53 tetramerization. Oncogene 7: 1513–1523, 1992

    Google Scholar 

  30. Sahulian E, Zauberman J, Milner J, Davies EA, Oren M: Tight DNA binding and oligomerization are dispensable for the ability of p53 to transactivate target genes and suppress transformation. EMBO J 12: 2789–2797, 1993

    Google Scholar 

  31. Wang Y, Reed M, Wang P, Stenger JE, Mayr G, Anderson ME, Schwedes JF, Tegtmeyer P: p53 domains: identification and characterization of two autonomous DNA-binding regions. Genes Dev 7: 2575–2586, 1993

    Google Scholar 

  32. Cho Y, Gorina S, Jeffrey PD, Pavletich NP: Crystal structure of a p53 tumor suppressor-DNA complex: Understanding tumorigenic mutations. Science 265: 346–355, 1994

    Google Scholar 

  33. Clore GM, Omichinski JG, Sakuguchi K, Zambrano N, Sakamoto H, Appella E, Gronenborn AM: High resolution structure of the oligomerization domain of p53 by multidimension NMR. Science 265: 386–391, 1994

    Google Scholar 

  34. Friend S: p53: A glimpse at the puppet behind the shadow play. Science 265: 334–335, 1994

    Google Scholar 

  35. Prives C: How loops, β sheets, and α helices help us to understand p53. Cell 78: 543–546, 1994

    Google Scholar 

  36. Santhanam U, Ray A, Sehgal PB: Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product. Proc Natl Acad Sci (USA) 88: 7605–7609, 1991

    Google Scholar 

  37. Weintraub HS, Hauschka S, Tapscott S: The MCK enhancer contains a p53 responsive element. Proc Natl Acad Sci (USA) 88: 4570–4571, 1991

    Google Scholar 

  38. Momand J, Zambetti GP, Olson DC, George D, Levine AJ: The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237–1245, 1992

    Google Scholar 

  39. Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace Jr AJ: A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71: 587–597, 1992

    Google Scholar 

  40. Smith ML, Chen IT, Zhan Q, Bae I, Chen C-Y, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr: Interaction of the p53-regulated protein GADD45 with proliferating cell nuclear antigen. Science 266: 1376–1380, 1994

    Google Scholar 

  41. Cahilly-Synder L, Yang-Fent T, Francke U, George DL: Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat Cell Mol Genet 13: 235–244, 1987

    Google Scholar 

  42. Fakharzadeh SS, Trusko SP, George DL: Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J 10: 1565–1569, 1991

    Google Scholar 

  43. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B: Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358: 80–83, 1992

    Google Scholar 

  44. Lavigeur A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A: High incidence of lung, bone, and lymphoid tumours in transgenic mice overexpressing mutant alleles of the p53 oncogene. Mol Cell Biol 9: 3982–3991, 1989

    Google Scholar 

  45. Donehower LA, Harvey M, Slogle BL, McArthur MJ, Montgomery CA, Butel JS, Bradley A: Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356: 215–222, 1992

    Google Scholar 

  46. Li FP, Fraumeni JF, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW: A cancer family syndrome in twenty-four kindreds. Cancer Res 48: 5358–5362

  47. Malkin D, Li FP, Strong LC, Fraumeni Jr JF, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, Friend SH: Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233–1238, 1990

    Google Scholar 

  48. Srivasatva A, Zou ZQ, Pirollo K, Blattner WA, Chang EH: Germline transmission of a mutated p53 gene in a cancerprone family with Li-Fraumeni syndrome. Nature 348: 747–749, 1990

    Google Scholar 

  49. Lavigeur A, Bernstein A: p53 transgenic mice: accelerated erythroleukemia induction by Friend virus. Oncogene 6: 2197–2201, 1991

    Google Scholar 

  50. Lee JM, Abrahamson JLA, Kandel R, Donehower LA, Bernstein A: Susceptibility to radiation-carcinogenesis and accumulation of chromosomal breakage in p53 deficient mice. Oncogene 9: 3731–3736, 1994

    Google Scholar 

  51. Kemp CJ, Wheldon T, Balmain A: p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis. Nature Genet 8: 66–69, 1994

    Google Scholar 

  52. Kemp CJ, Donehower LA, Bradley A, Balmain A: Reduction of p53 gene dosage does not increase initiation or promotion but enhances malignant progression of chemically induced skin tumours. Cell 74: 813–822, 1993

    Google Scholar 

  53. Harvey M, McArthur MJ, Montgomery CA, Butel JS, Bradley A, Donehower LA: Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice. Nature Genet 5: 225–229, 1993

    Google Scholar 

  54. Dittmer S, Pati S, Zambetti G, Chu S, Teresky AK, Moore M, Foster D, Anderson RJ, Levine AJ: Gain of function mutations in p53. Nature Genetics 4: 42–46, 1993

    Google Scholar 

  55. Harvey M, Vogel H, Morris D, Bradley A, Bernstein A, Donehower LA: A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice. Nature Genetics 9: 305–311, 1995

    Google Scholar 

  56. Lee JM, Abrahamson JLA, Bernstein A: DNA damage, oncogenesis, and the p53 tumour suppressor. Mutation Res 307: 573–581, 1994

    Google Scholar 

  57. Norbury C, Nurse P: Animal cell cycles and their control. Ann Rev Biochem 61: 441–470, 1992

    Google Scholar 

  58. Reed S: The role of p34 kinases in the G1 to S-phase transition. Ann Rev Cell Biol 8: 529–562, 1992

    Google Scholar 

  59. Sherr CJ: Mammalian G1 cyclins. Cell 73: 1059–1065, 1993

    Google Scholar 

  60. Keyomarsi K, Pardee AB: Rebundant cyclin overexpression and gene amplification in breast cancer cells. Proc Natl Acad Sci (USA) 90: 1112–1116, 1993

    Google Scholar 

  61. Leach FS, Elledge SJ, Sherr CJ, Wilson JK, Markowitz S, Kinzler KW, Vogelstein B: Amplification of cyclin genes in colorectal carcinomas. Cancer Res 53: 1986–1989, 1993

    Google Scholar 

  62. Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A: A novel cyclin encoded by a bc11-linked candidate oncogene. Nature 350: 512–515, 1991

    Google Scholar 

  63. Withers DA, Harvey RC, Faust JB, Melnyk O, Carey K, Meeker TC: Characterization of a candidate bcl-1 gene. Mol Cell Biol 11: 4846–4853, 1991

    Google Scholar 

  64. Seto M, Yamamoto K, Iida S, Akao Y, Utsum 1 KR, Kubonishi I, Miyoshi I, Ohtsuki T, Yawatta Y, Namba M, Motokura T, Arnold A, Takahashi T, Ueda R: Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy. Oncogene 7: 1401–1406, 1992

    Google Scholar 

  65. Hartwell LH, Weinert TA: Checkpoints: Controls that ensure the order of cell cycle events. Science 629–634, 1989

  66. Weinert TA, Hartwell LH: The RAD9 gene controls the cell cycle response to DNA damage inSaccharomyces cerevisiae. Science 241: 317–322, 1988

    Google Scholar 

  67. Lock RB, Ross WE: Inhibition of p34cdc2 kinase activity by ectoposide or irradiation as a mechanisms of G2 arrest in Chinese hamster ovary cells. Cancer Res 50: 3761–3766, 1990

    Google Scholar 

  68. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW: Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51: 6304–6311, 1991

    Google Scholar 

  69. Lu X, Lane DP: Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell 75: 765–778, 1993

    Google Scholar 

  70. Nelson WG, Kastan M: DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways. Mol Cell Biol 14: 1815–1823, 1994

    Google Scholar 

  71. Dulic V, Kaufmann WK, Wilson SJ, Tlsty TD, Lees E, Harper JW, Elledge SJ, Reed SI: p53 dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76: 1013–1023, 1994

    Google Scholar 

  72. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge S: The p21 Cdk-interaction protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805–816, 1993

    Google Scholar 

  73. Xiong Y, Khang H, Beach D: p21 is a universal inhibitor of cyclin kinases. Nature 366: 701–704, 1993

    Google Scholar 

  74. Gu Y, Turck CW, Morgan DO: Inhibition of Cdk2 activityin vivo by an associated 20K regulatory subunit. Nature 366: 707–710, 1993

    Google Scholar 

  75. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer E, Kinzler KW, Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell 75: 817–825, 1993

    Google Scholar 

  76. Noda A, Ning Y, Venable SF, Pereira OM, Smith JR: Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res 211: 90–98, 1994

    Google Scholar 

  77. Ohtsubo M, Roberts JM: Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science 259: 1908–1912, 1993

    Google Scholar 

  78. El-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Kohn KW, Elledge SJ, Kinzler KW, Vogelstein B: WAF1/CIPI is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54: 1169–1174, 1994

    Google Scholar 

  79. Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB: Wildtype p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci (USA) 89: 7491–7495, 1992

    Google Scholar 

  80. Waga S, Hannon GJ, Beach D, Stillman B: The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369: 574–578, 1994

    Google Scholar 

  81. Prelich G, Kostura M, Marshak DR, Mathews MB, Stillman B: The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replicationin vitro. Nature 326: 471–475, 1987

    Google Scholar 

  82. Shivji MKK, Kenny MK, Wood RD: Proliferating cell nuclear antigen is required for DNA excision repair. Cell 69: 367–374, 1992

    Google Scholar 

  83. Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD: Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70: 923–936, 1992

    Google Scholar 

  84. Yin Y, Tainsky MA, Bischoff FZ, Strong LC, Wahl GM: Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 70: 937–948, 1992

    Google Scholar 

  85. Harvey M, Sands AT, Weiss RS, Hegi ME, Wiseman RW, Pantazis P, Giovanella BC, Tainsky MA, Bradley A, Donehower LA:In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice. Oncogene 8: 2457–2467, 1993

    Google Scholar 

  86. Gatti RA, Boder E, Vinters HV, Sparkes RS, Norman A, Lange K: Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis. Medicine 70: 99–117, 1991

    Google Scholar 

  87. McKinnon PJ: Ataxia-telangiectasia; an inherited disorder of ionizing-radiation sensitivity in man. Hum Genet 75: 197–208, 1987

    Google Scholar 

  88. Painter RB, Young BR: Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc Natl Acad Sci (USA) 77: 7315–7317, 1980

    Google Scholar 

  89. Fornace AJ Jr, Nebert DW, Hollander MC, Luethy JD, Papthanasiou M, Fargnoli J, Holbrook NJ: Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents. Mol Cell Biol 9: 4196–4203, 1989

    Google Scholar 

  90. Papathanasiou MA, Kerr NC, Robbins JH, McBride OW, Alamo IJ, Barrett SF, Hickson ID, Fornace AJ Jr: Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C. Mol Cell Biol 11: 1009–1016, 1991

    Google Scholar 

  91. Li R, Waga S, Hannon GJ, Beach D, Stillman B: Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature 371: 534–537, 1994

    Google Scholar 

  92. Lee JM, Bernstein A: p53 mutations increase resistance to ionizing radiation. Proc Natl Acad Sci (USA) 90: 5742–5746, 1993

    Google Scholar 

  93. Xu Z, Lane DP: Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes. Cell 75: 765–778, 1993

    Google Scholar 

  94. Cohen JJ, Duke RC, Fadok VA, Sellins KS: Apoptosis and programmed cell death in immunity. Ann Rev Immunol 10: 267–293, 1992

    Google Scholar 

  95. Vaux DL, Haecker G, Strasser A: An evolutionary perspective on apoptosis. Cell 76: 777–779, 1994

    Google Scholar 

  96. Sellins KS, Cohen JJ: Gene induction by γ-irradiation leads to DNA fragmentation in lymphocytes. J Immunol 139: 3199–3206, 1987

    Google Scholar 

  97. Fisher DE: Apoptosis in therapy: crossing the threshold. Cell 78: 539–542, 1994

    Google Scholar 

  98. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T: p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362: 847–849, 1993

    Google Scholar 

  99. Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, Wylie AH: Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362: 849–852, 1993

    Google Scholar 

  100. Lowe SW, Ruley HE, Jacks T, Housman DE: p53-mediated apoptosis modulates the cytotoxicity of anticancer agents. Cell 74: 957–967, 1993

    Google Scholar 

  101. Caelles C, Helmberg A, Karin M: p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 370: 220–223, 1994

    Google Scholar 

  102. Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M: Wild-type p53 induces apoptosis of myeloid leukemia cells that is inhibited by interleukin-6. Nature 352: 345–347, 1991

    Google Scholar 

  103. Johnson P, Chung S, Benchimol S: Growth suppression of Friend-virus-transformed erythroleukemia cells by p53 protein is accompanied by hemoglobin production and is sensitive to erythropoietin. Mol Cell Biol 13: 1456–1463, 1993

    Google Scholar 

  104. McWhir JM, Selfridge J, Harrison DJ, Squires S, Melton DW: Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Nature Genetics 5: 217–224, 1993

    Google Scholar 

  105. Devary Y, Gottlieb GT, Smeal T, Karin M: The mammalian ultraviolet response is triggered by activation of src tyrosine kinases. Cell 71: 1081–1092, 1993

    Google Scholar 

  106. Devary Y, Rosette C, DiDonato JA, Karin M: NF-kappa B activation by ultraviolet light not dependent on a nuclear signal. Science 261: 1442–1445, 1993

    Google Scholar 

  107. Uckun FM, Tuel-Ahlgren L, Song CW, Waddick K, Myers DE, Kirihara J, Ledbetter JA, Schieven GL: Ionizing radiation stimulates unidentified tyrosine-specific protein kinases in human B-lymphocyte precursors, triggering apoptosis and clonogenic cell death. Proc Natl Acad Sci (USA) 89: 9005–9009, 1992

    Google Scholar 

  108. Bischoff JR, Friedman PN, Marshak DR, Prives C, Beach D: Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. Proc Natl Acad Sci (USA) 87: 4766–4770, 1990

    Google Scholar 

  109. Shi L, Hishioka WK, Th'ng J, Bradbury EM, Litchfield DW, Greenberg AH: Premature p34cdc2 activation required for apoptosis. Science 263: 1143–1145, 1994

    Google Scholar 

  110. Kharbanda S, Saleem A, Datta R, Yuan Z-M, Weichselbaum R, Kufe D: Ionizing radiation induces rapid tyrosine phosphorylation of p34cdc2. Cancer Res 54: 1412–1414, 1994

    Google Scholar 

  111. Symonds H, Krall L, Remington L, Saenz-Robles, Lowe S, Jacks T, Van Dyke T: p53-dependent apoptosis suppresses tumor growth and progressionin vivo. Cell 78: 703–712, 1994

    Google Scholar 

  112. Bardeessy N, Falkoff D, Petruzzi M-J, Nowak N, Zabel B, Adam M, Aguiar MC, Grundy P, Shows T, Pelletier J: Anaplastic Wilms' tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nature Gen 7: 91–97, 1994

    Google Scholar 

  113. Wada M, Bartram CR, Nakamura H, Hachiya M, Chen D-L, Borenstein J, Miller CW, Ludwig L, Hansen-Hagge TE, Ludwig W-D, Reiter A, Mizoguchi H, Koeffler HP: Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood. Blood 82: 3163–3169, 1993

    Google Scholar 

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Lee, J.M., Bernstein, A. Apoptosis, cancer and the p53 tumour suppressor gene. Cancer Metast Rev 14, 149–161 (1995). https://doi.org/10.1007/BF00665797

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