p53-dependent cell cycle control: Response to genotoxic stress

Seminars in Cancer Biology

Volumn 8, Issue 5, 1998, Pages 325-336

  Schwartz, Dov ^b   Rotter, Varda ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b NONE

Author keywords

Apoptosis; Genotoxic stress; p53; Tumour suppressor function

Indexed keywords

PROTEIN P53;

ANIMAL CELL; APOPTOSIS; CARCINOGENESIS; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE S PHASE; CELL DIVISION; CHROMOSOME CONDENSATION; CONTROLLED STUDY; DNA DAMAGE; DNA REPAIR; GENE LOCATION; GENOME; GENOTOXICITY; MITOSIS; MOUSE; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

EID: 0031987296     PISSN: 1044579X     EISSN: None     Source Type: Journal    
DOI: 10.1006/scbi.1998.0095     Document Type: Article

References (172)

1. 1. Lane DP (1992) p53, guardian of the genome. Nature 358:15-16
2. 2. Fukasawa K, Wiener F, Vande Woude GF, Mai S (1997) Genomic instability and apoptosis are frequent in p53 deficient young mice. Oncogene 15:1295-1302
3. 3. Lu X, Lane DP (1993) Differential induction of transcriptionally active p53 following UV or ionizing irradiation: Defects in chromosome instability syndromes? Cell 75:765-778
4. 4. Livingstone LR, White A, Sprouse I, Livanos E, Jacks T, Tisty TD (1992) Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70:923-935
5. 5. Hartwell L (1992) Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. Cell 71:543-546
6. 6. Gottlieb TM, Oren M (1996) p53 in growth control and neoplasia. Biochem Biophys Acta Rev Cancer 1287:77-102
7. 7. Levine JA (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323-331
8. 8. Chen X, Ko LJ, Jayaraman L, Prives C (1996) p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10:2438-2451
9. 9. Almog N, Rotter V (1997) Involvement of p53 in cell differentiation and Development. Biochem Biophys Acta 1333:F1-F27
10. 10. Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunket BS, Vogelstein B, Fornace AJ (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in Ataxia-Telangiectasia. Cell 71:587-597
11. 1 arrest. Cell 76:1013-1023
12. 1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc Natl Acad Sci USA 92:8493-8497
13. 2-dependent immunoglobulin k light chain gene expression. EMBO J 14:1392-1401
14. 2 checkpoint function in cells from individuals with familial cancer syndromes. Cancer Res 55:1763-1773
15. 15. Cross SM, Sanchez CA, Morgan CA, Schimke MK, Ramel S, Idzerda RL, Raskind WH, Reid BJ (1995) A p53-dependent mouse spindle checkpoint. Science 267:1353-1356
16. 16. Golsteyn RM, Mundt KE, Fry AM, Nigg EA (1995) Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function. J Cell Biol 129(6):1617-1628
17. 17. Wells WAE (1996) The spindle-assembly checkpoint: aiming for a perfect mitosis, every time. Trends Cell Biol 6:228-234
18. 18. Bates S, Vousden KH (1996) p53 in signaling checkpoint arrest or apoptosis. Curr Opin Genet Dev 6:12-19
19. 2 checkpoint function precedes human immortalisation. Cancer Res 55:7-11
20. 20. Wang XW, Vermwulen M, Coursen JD, Gibson M, Lupold SE, Forrester K, Xu G, Elmore L, Yeh H, Hoeijmakers JHJ, Harris CC (1996) The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Gen Devel 10:1219-1232
21. 21. Dutta A, Ruppert JM, Aster JC, Wincherester E (1993) Inhibition of DNA replication factor RPA by p53. Nature 365:79-82
22. 22. Sturzbecher H-W, Donzelmann B, Henning W, Knippschild U, Buchhop (1996) p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction. EMBO J 15:1992-2002
23. 23. Lim D, Hasty P (1996) A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Mol Cell Biol 16:7133-7143
24. 24. Gervais JLM, Seth P, Zhang H (1998) Cleavage of CDK inhibitor p21(cip1/waf1) by caspases is an early event during DNA damage-induced apoptosis. J Biol Chem 273: 19207-19212
25. 25. An B, Dou QP (1996) Cleavage of retinoblastoma protein during apoptosis: an interleukin 1 β-converting enzyme-like protease as candidate. Cancer Res 56:438-442
26. 26. Janicke RU, Walker PA, Lin XY, Porter AG (1996) Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis. EMBO J 15:6969-6978
27. 1 protects cells from apoptosis induced by UV-irradiation of RNA polymerase II blockage. Oncogene 16:3461-3469
28. 28. Agarwal ML, Agarwal A, Taylor WR, Wang ZQ Wagner EF, Stark GR (1997) Defective induction but normal activation and function of p53 in mouse cells lacking poly-ADP-ribose polymerase. Oncogene 15:1035-1041
29. 29. Barak Y, Juven T, Haffner R, Oren M (1993) Mdm2 expression is induced by wild-type-p53 activity. EMBO J 12:461-468
30. 30. Haupt Y, Maya R, Kazak A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387:296-299
31. 31. Kubbutat MHG, Jones SN, Vousden KH (1997) Regulation of p53 stability by Mdm2. Nature 387:299-303
32. 32. Lane DP, Hall PA (1997) MDM2-arbiter of p53's destruction. TIBS 22:372-374
33. 33. Roth I, Dobbelstein M, Freedman DA, Shenk T, Levine AJ (1998) Nuclear-cytoplasmatic shuttling of the hmd2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein. EMBO J 17:554-564
34. 34. Nelson WG, Kastan MB (1994) DNA strand breaks - the DNA template alteration that triggers p53 dependent DNA damage response pathways. Mol Cell Biol 14:1815-1823
35. 35. Kastan MR, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304-6311
36. 36. Lee JM, Bernstein A (1993) p53 mutations increase resistance to ionizing irradiation. Proc Natl Acad Sci USA 90:5742-5746
37. 37. Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB (1992) Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 89:7491-7495
38. 38. Maltzman W, Czyzyk L (1984) UV irradiation stimulates levels of p53 cellular tumor antigen in non-transformed mouse cells. Mol Cell Biol 4:1689-1694
39. 39. Hall PA, McKee PH, Menage Hd-P, Dover R, Lane DP (1993) High levels of p53 protein in UV-irradiated normal human skin. Oncogene 8:203-207
40. 40. Hall PA, McKee PH, Menage HD, Dover R, Lane DP (1993) High levels of p53 protein in UV-irradiated normal human skin. Oncogene 8:203-207
41. 41. Yamaizumi M, Sugano T (1994) UV-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle. Oncogene 9:2775-2784
42. 42. Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Ponten J (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA 88:10124-10128
43. 43. Zhan Q Carrier F, Fornace AJ (1993) Induction of cellular p53 activity by DNA-damaging agents and growth arrest. Mol Cell Biol 13:4242-4250
44. 44. Tishler RB, Calderwood SK, Coleman CN, Price BD (1993) Increases in sequence-specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. Cancer Res 53:2212-2216
45. 45. Herrlich P, Rahmsdorf HJ (1994) Transcriptional and post-transcriptional responses to DNA-damaging agents. Curr Opin Cell Biol 6:425-431
46. 46. Pritsche M, Haessler C, Brander G. (1993) Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. 8:307-318
47. 47. An WG, Kanekal M, Simon MC, Maltepe E, Blagosklony MV, Neckers LM (1998) Stabilization of wild-type p53 by hypoxia-inducible factor 1 α. Nature 392:405-408
48. 48. Graeber T, Osmanian C, Jacks T, Housman D, Koch C., Lowe SM, Giaccia AJ (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379:88-91
49. 49. Yin Y, DeWolf WC, Morgentaler A (1998) Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice. Biol Reprod 58:492-496
50. 50. Matsumoto H, Takahashi A, Wang X, Ohnishi K, Ohnishi T. (1997) Transfection of p53-knockout mouse fibroblasts with wild-type p53 increases the thermosensitivity and stimulates apoptosis induced by heat stress. Int J Radiat Oncol Biol Phys 39:197-203
51. 51. Wu L, Bayle H, Elenbaas B, Pavletich NP, Levine AJ (1995) 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 15:497-504
52. 52. Jayaraman L, Prives C (1995) Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus. Cell 81:1021-1029
53. 53. Lee S, Elenbaas B, Levine A, Griffith J (1995) p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell 81: 1013-1020
54. 54. Reed W, Woelker B, Wang P, Wang Y, Anderson ME, Tegtmeyer P (1995) The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation. Proc Natl Acad Sci USA 92:9455-9459
55. 55. Wang XW, Yeh H, Schaeffer L, Roy R, Moncolli V, Egly J-M, Wang Z, Friedberg EC, Evans MK, Taffe BG, Bohr VA, Weeda G, Hoeijmakers JHJ, Forrester K, Harris CC (1995) p53 modulation of TFIIH-associated nucleotide excision repair activity. Nat Genet 10:188-195
56. 56. Ford JM, Hanawalt PC (1997) Expression of wild-type p53 is required for efficient global genomic nucleotide excision repair in UV-irradiated human fibroblasts. J Biol Chem 272:28073-28080
57. 57. Barlow C, Liyanage M, Moens PB, Deng C-X, Ried T, Wynshaw-Boris A (1997) Partial rescue of the prophase 1 defects of Atm-deficient mice by p53 and p21 null alleles. Nat Genet 17:462-466
58. 58. Banin S, Moyal L, Shieh S-Y, Anderson CM, Chessa L, Smorodinsky NI, Prives C, Shiloh Y, Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science in press
59. 59. Waterman MJF, Stavridi ES, Waterman JLF, Halazonetis TD (1998) ATM-dependent activation of p53 involves dephosphorylation and association with 14-4-3 proteins. Nat Genet 19:175-178
60. 60. Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley NJ, Ried T, Tagle D, Wynshaw-Boris A (1996) Atm deficient mice: a paradigm of Ataxia Telangiectasia. Cell 86:159-171
61. 61. Enoch T, Norbury C (1995) Cellular responses to DNA damage: cell-cycle checkpoints, apoptosis and the roles of p53 and ATM. TIBS 20:426-434
62. 62. Hawley RS, Friend SH (1996) Strange bedfellows in even stranger places: the role of ATM in meiotic cells, lymphocytes, tumors, and its functional links to p53. Genes Dev 10:2382-2388
63. 63. Xu Y, Baltimore D (1996) Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev 10:2401-2410
64. 64. Xu Y, Ashley T, Brainerd EE, Bronson RT, Meyn MS, Baltimore D (1996) Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev 10: 2411-2422
65. 65. Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BI, El-Deiry WS (1998) BRCA1 physically associates with p53 and stimulates its transcriptional activity. Oncogene 16:1713-1721
66. 66. Chen I-T, Smith ML, O'Connor PM, Fornace AJJ (1995) Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p211Waf1/Cip1 with PCNA. Oncogene 11:1931-1937
67. 67. Flores-Rozas H, Kelman Z, Dean F, Pau Z, Harper W, Elledge S, O'Donnell M, Hurowitz J (1994) CDK interacting protein directly binds with PCNA and inhibits DNA replication catalyzed by polymerase d holoenzyme. Proc Natl Acad Sci USA 91:8655-8659
68. 68. Shivji M, Grey S, Strausfeld U, Wood R, Blow J (1994) Cip1 inhibits DNA replication but not PCNA-dependent nucleotide excision-repair. Curr Biol 4:1062-1068
69. 69. Haldar S, Negrini M, Monne W, Sabbioni S, Croce CM (1994) Downregulation of bcl-2 by p53 in breast cancer cells. Cancer Res 54:2095-2097
70. 70. Beham A, Marin MC, Fernandez A, Herrmann I, Brisbay S, Tari AM, Lopez-Berestein G, Lozano G, Sarkiss M, McDonnell TJ (1997) Bcl-2 inhibits p53 nuclear import following DNA damage. Oncogene 15:2767-2772
71. 71. Marin MC, Hsu B, Meyn RE, Donehower LA, El-Naggar AK, McDonnell TA (1994) Evidence that p53 and bcl-2 are regulators of a common cell death pathway important for in vivo lymphomagenesis. Oncogene 9:3107-3112
72. 72. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA (1994) Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799-1805
73. 1: a paradigm for distinct apoptotic pathways. Oncogene 9:1791-1798
74. 74. Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293-299
75. 75. Merchant AK, Loney TL, Maybaum J (1996) Expression of wild-type p53 stimulates an increase in both Bax and Bcl-x1 protein content in HT29 cells. Oncogene 13:2631-2637
76. 76. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75:817-825
77. 77. El-Deiry W, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B (1992) Definition of a consensus binding site for p53. Nat Genet 1:45-49
78. 2/M progression. Mol Cell 1:3-11
79. 79. Zhan Q, Bae I, Kastan MB, J FA (1994) The p53-dependent γ-ray response of GADD45. Cancer Res 54:2755-2760
80. 80. Okamoto K, Beach D (1994) Cyclin G is a transcriptional target of the p53 tumor suppressor protein. The EMBO J 13:4816-4822
81. 81. Zauberman A, Lupo A, Oren M. (1995) Identification of p53 target genes through immune selection of genomic DNA: the cyclin G gene contains two distinct p53 binding sites. Oncogene 10:2361-2366
82. 82. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362:847-853
83. 83. Rowan S, Ludwig RL, Haput Y, Bates S, Lu X, Oren M, Vousden KH (1996) Specific loss of apoptotic but not cell-cycle arrest function in a human tumor derived p53 mutant. EMBO J 15:827-838
84. 84. Gualberto A, Aldape K, Kozakiewicz K, Tisty TD (1998) An oncogenic form of p53 confers a dominant, gain-of-function phenotype that disrupts spindle check point control. Proc Natl Acad Sci USA 95:5166-5171
85. 85. Donehower LA, Harvey M, Slagle BT, McArthur MJ, Montgomery CA, Butel JS, Bradly A (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors. Nature 356:215-221
86. 86. Gondo Y, Nakamura K, Nakao K, Sasacka T, Ito K, Kimura M, Katsuki M. (1994) Gene replacement of the p53 gene with the lacZ gene in mouse embryonic stem cells and mice by using two steps of homologous recombination. Biochem Biophys Res Commun 202:830-837
87. 87. Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT, Weinberg RA (1994) Tumor spectrum analysis in p53-mutant mice. Curr Biol Curr Biol 4:1-7
88. 88. Norimura T, Nomoto S, Katsuki M, Gondo Y, Kondo S (1996) p53 dependent apoptosis suppresses radiation-induced teratogenesis. Nature Med 2:577-580
89. 89. Nicol CJ, Harrison ML, Laposa RR, I.L. G, Wells PG (1995) A teratologic suppressor role for p53 in benzo[a]pyrene-treated transgenic p53 deficient mice. Nat Genet 10:181-186
90. 90. Aladjem MI, Spike BT, Rodewald LW, Hope TJ, Klemm M, Jaenisch R, Wahl GM (1998) ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage. Curr Biol 8:145-55
91. 91. Prost S, Bellamy CO, Clarke AR, A.H. W, Harrison DJ (1998) p53 independent DNA repair and cell cycle arrest in embryonic stem cells. FEBS Lett 425:499-504
92. 92. Schmidt-Kastner PK, Jardine K, Cormier M, McBurney MW (1998) Absence of p53-dependent cell cycle regulation in pluripotent mouse cell lines. Oncogene 16:3003-3011
93. 93. Bouffler SD, Kemp CJ, Balmain A, Cox R (1995) Spontaneous and ionizing radiation-induced chromosomal abnormalities in p53-deficient mice. Cancer Res 55:3883-3889
94. 94. Ohashi M, Hatakeyama K, Aizawa S, Kominami R (1998) P53 gene deficiency does not enhance instability of mouse mini-satellites in somatic cells of normal tissues. Jpn J Cancer Res 87:696-670
95. 95. Buettner VL, Nishino H, Haavik J, Knoll A, Hill K, Sommer SS (1997) Spontaneous mutation frequencies and spectra in p53 (+/+) and p53 (-/-) mice: a test of the 'guardian of the genome' hypothesis in the BigBlue transgenic mouse mutation detection system. Mutat Res 379:13-20
96. 96. Hundley JE, Koester SK, Troyer DA, Hilsenbeck SG, Barrington RE, Windle JJ (1997) Differential regulation of cell cycle characteristics and apoptosis in MMTV-myc and MMTV-ras mouse mammary tumors. Cancer Res 57:600-603
97. 97. Ford JM, Hanawalt PC (1995) Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in global DNA repair but enhanced UV-resistance. Proc Nat Acad Sci USA 92:8876-8890
98. 98. Mallya SM, MO S (1998) Evidence for the involvement of p53 in γ radiation-induced DNA repair in human lymphoblasts. Int J Radiat Biol 74:231-238
99. 99. Lee JM, Abramson JL, Kandel R, Donehower LA, Bernstein A (1994) Susceptibility to radiation-carcinogenesis and accumulation of chromosomal breakage in p53 deficient mice. Oncogene 9:3731-3736
100. 100. Schwartz D, Almog N, Peled A, Goldfinger N, Rotter V (1997) Role of wild-type p53 in the G2 phase: regulation of the γ-irradiation-induced delay and DNA repair. Oncogene 15:2597-2607
101. 101. Symonds H, Krall L, Remington L, Saenz-Robles M, Lowe S, Jacks T, Van Dyke T (1994) p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 78:703-711
102. 102. Jones JM, Attardi L, Godley LA, Laucirica R, Medina D, Jacks T, Varmus HE, Donehower LA (1997) Absence of p53 in a mouse mammary tumor model promotes tumor cell proliferation without affecting apoptosis. Cell Growth Differ 8:829-838
103. 103. Yang T, Namba H, Kara T, Takmura N, Nagayama Y., Fukata S, Ishikawa N, Kuma K, Ito K, Yamashita S. (1997) p53 induced by ionizing radiation mediates DNA end-jointing activity, but not apoptosis of thyroid cells. Oncogene 14:1511-1519
104. 104. Williams KJ, Boyle JM, Birch JM, Norton JD, Scott D (1997) Cell cycle arrest defect in Li-Fraumeni Syndrome: a mechanism of cancer predisposition? Oncogene 14:277-282
105. 105. Delia D, Goi K, Mizutani S, Yamada T, Aiello A, Fontanella E, Lamorte G, Iwata S, Ishioka C, Krajewski S, Reed JC, Pierotti MA (1997) Dissociation between cell cycle arrest and apoptosis can occur in Li-Fraumeni cells heterozygous for p53 gene mutations. Oncogene 14:2137-2147
106. 106. Goi K, Takagi M, Iwata S, Delia D, Asada M, Donghi R, Tsunematsu Y, Nakazawa S, Yamamoto H, Yokota J, Tamura K, Saeki Y, Utsunomiya J, Takahashi T, Ueda R, Ishioka C, Eguchi M, Kamata N, Mizutani S (1997) DNA damage-associated dysregulation of the cell cycle and apoptosis control in cells with germ-line p53 mutation. Cancer Res 57:1895-1902
107. 2-phase X irradiation in relation to DNA repair and radiosensitivity in a cancer-prone family with Li-Fraumeni syndome. Radiat Res 136:236-240
108. 108. Wolf D, Harris N, Rotter V (1984) Reconstitution of p53 expression in a non-producer Ab-MuLV-transformed cell line by transfection of a functional p53 gene. Cell 38:119
109. 109. Jenkins JR, Rudge K, Currie GA (1984) Cellular immortalisation by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature 312:651-654
110. 110. Parada L, Land F, Weinberg A, Wolf D, Rotter V (1984) Cooperation between the gene encoding the p53 tumor antigen and Ras in cellular transformation. Nature 312:649-651
111. 111. Eliyahu D, Raz A, Gruss P, Givol D, Oren M (1984) Participation of p53 cellular tumor antigen in transformation of normal embryonic cells. Nature 312:646-649
112. 112. Chen Y, Bookstein R, Lee W-L (1991) Genetic mechanisms of tumor suppression by the human p53 gene. Science 250:1576-1580
113. 113. Baker SJ, Markowite S, Fearon ER, Wilson JKV and Vogelstein B (1990) Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249:912-915
114. 114. Dittmer D, Pati S, Zambetti G, Chu S, Teresky A, Moore M, Finlay C, Levine A (1993) Gain of function mutations in p53. Nat Genet 4:42-46
115. 115. Lavigueur A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A (1989) High incidence of lung, bone, and lymphoid tumors in transgenic mice over-expressing mutant alleles of the p53 oncogene. Mol Cell Biol 9:3982-3991
116. 116. Harvey M, Vogel H, Morris D, Bradley A, Bernstein A, Donehower LA (1995) A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice. Nat Genet 9:305-311
117. 117. Wu MC, Sundaresan M, Sundaresan V, Rabbitts P (1997) Genome wide search for genetic damage in p53 transgenic mouse lung tumours reveals consistent loss of chromosome 4. Eur J Cancer 33:1677-1684
118. 118. Li B, Greenberg N, Stephens LC, Meyn R, Medina D, Rosen JM (1994) Preferential over-expression of a 172Arg → Leu mutant p53 in the mammary gland of transgenic mice results in altered lobuloalveolar development. Cell Growth Differ 5:711-721
119. 119. Li B, Rosen JM, McMenamin-Balano J, Muller WJ, Perkins AS (1997) neu/ERBB2 cooperates with p53-172H during mammary tumorigenesis in transgenic mice. Mol Cell Biol 17:3155-3163
120. 120. Peled A, Schwartz D, Elkind NB, Wolkowicz R, Li R, Rotter V (1996) The role of p53 in the induction of polyploidity of myelomonocytic leukemic M1/2 cells. Oncogene 13: 1677-1685
121. 121. Li R, Sutphin PD, Schwartz D, Matas D, Almog N, Wolkowicz R, Goldfinger N, Huiping R, Prokocimer M, Rotter V (1998) Mutant p53 protein expression interferes with p53-independent apoptotic pathways. Oncogene 16:3269-3277
122. 122. Knudson CM, Tung KS, Tourtellotte WG, Brown GA, Korsmeyer SA (1995) Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270:96-99
123. 123. Oltvai ZN, Milliman CL, Korsmeyer SA (1993) bcl-2 heterodimerizes in vivo with a conserved homolog, bax, that accelerates programmed cell death. Cell 74:609-619
124. 124. Zhan Q, Fan S, Bae L, Guillouf C, Lieberman DA, O'Connor PM, Fornace AJ Jr (1994) Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene 9:3743-3751
125. 125. Jost CA, Marin MC, Kaelin WG Jr (1997) p73 is a human p53-related protein that can induce apoptosis. Nature 389:191-194
126. 1 arrest and apoptosis. Cancer Res 54:1169-1174
127. 1 cyclin-dependent kinases. Cell 75:805-816
128. 2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol Cell Biol 18:629-643
129. 1 checkpoint control. Cell 82:675-684
130. 130. Wang YA, Elson A, Leder P (1997) Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice. Proc Natl Acad Sci USA 94:14590-14595
131. 2 checkpoint function precedes human cell immortalization. Cancer Res 55:7-11
132. 2 regulatory genes and their possible involvement in genetic instability in cancer cells. Princess Takamatsu Symp 22:231-238
133. 133. Hoffmann IC, PR, Marcote MJ, Karsenti E, Draetta G (1993) Phosphorylation and activation of human cdc25-C by cdc2-cyclin B and its involvement in the self-amplification of MPF at mitosis. EMBO J 12:53-63
134. 134. Poon RY, Chau MS, Yamashita K, Hunter T (1997) The role of Cdc2 feedback loop control in the DNA damage checkpoint in mammalian cells. Cancer Res 57:5168-5178
135. 135. Berry LD, Gould KL (1996) Regulation of Cdc2 activity by phosphorylation at T14/Y15. Prog Cell Cycle Res 2:99-105
136. 136. Conklin DS, Galaktionov K, Beach D (1995) 14-3-3 proteins associate with cdc25 phosphatases. Proc Natl Acad Sci USA 92:7892
137. 2/M by p53. Oncogene 10:109-115
138. 1 cyclin-dependent kinases. Nature 376:88-91
139. 2 delay. Cancer Res 55:1643-1648
140. 2 arrest in human cells. Oncogene 17:673-684
141. 141. Brugarolas J, Chandrasekaran C, Gordon IJ, Beach D, Jacks T, Hannon JG (1995) Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377:552-557
142. 142. Medema RH, Klompmaker R, Smits VA, Rijksen G (1998) p21waf1 can block cells at two points in the cell cycle, but does not interfere with processive DNA-replication or stress-activated kinases. Oncogene 16:431-441
143. 2 cell cycle arrest in p53-deficient cells. Oncogene 16:311-320
144. 2 arrest after DNA damage. Science 282:1497-1501
145. 2/M arrest of cells in response to DNA damage. Biochem Biophys Res Commun 242:529-533
146. 146. Lowe SW, Jacks T, Housman DE, Ruley HE (1994) Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. Proc Natl Acad Sci USA 91:2026-2030
147. 2/M transition: abrupt breakdown of cytoplasmic microtubules at nuclear envelope breakdown and implications for spindle morphogenesis. J Cell Biol 135:201-214
148. 148. Andreassen PR, Martineau SN, Margolis RL (1996) Chemical induction of mitotic checkpoint override in mammalian cells results in aneuploidy following a transient tetraploid state. Mutat Res 3722
149. 149. Thomas JT, Laminis LA (1998) Human papillomavirus oncoproteins E6 and E7 independently abrogate the mitotic spindle checkpoint. J Virol 72:1131-1137
150. 150. Lanni JS, Lowe SW, Licitra EJ, Liu JO, Jacks T (1997) p53-independent apoptosis induced by paclitaxel through an indirect mechanism. Proc Nati Acad Sci USA 94: 9679-9683
151. 151. Chapman DL, Wolgemuth DJ (1994) Regulation of M-phase promoting factor activity during development of mouse male germ cells. Dev Biol 165:500-506
152. 152. Wu S, Wolgemuth DJ (1995) The distinct and developmentally regulated patterns of expression of members of the mouse Cdc25 gene family suggest differential functions during gametogenesis. Development 170:195-206
153. 153. Dix DJ, Allen JW, Collins BW, Poorman-Allen PMC, Blizard DR, Brown PR, Goulding EH, Strong BD, Eddy EM (1997) HSP70-2 is required for desynapsis of synaptonemal complexes during meiotic prophase in juvenile and adult mouse spermatocytes. Development 124:4595-4603
154. 154. Zhu D, Dix DJ, Eddy EM (1997) HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes. Development 124:3007-3014
155. 2/M-phase transition in pachytene spermatocytes includes events unique to meiosis. Dev Biol 169:557-567
156. 156. Almon E, Goldfinger N, Kapon A, Schwartz D, Levine AJ, Rotter V (1993) Testicular tissue-specific expression of the p53 suppressor gene. Dev Biol 156:107-116
157. 157. Schwartz D, Goldfinger N, Rotter V (1993) Expression of p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes. Oncogene 8:1487-1494
158. 158. Sjoblom T, Lahdetie J (1996) Expression of p53 in normal and gamma-irradiated rat testis suggests a role for p53 in meiotic recombination and repair. Oncogene 12:2499-2505
159. 159. Rotter V, Schwartz D, Almon E, Goldfinger N, Kapon A, Meshorer A, Donehower LA, Levine AJ (1993) Mice with reduced levels of p53 exhibit the testicular giant cell degenerative syndrome. Proc Natl Acad Sci USA 90:9075-9079
160. 160. Chresta CM, Hickman JA (1996) Oddball p53 in testicular tumors. Nat Med 2:745-746
161. 161. Chresta CM, Masters JRW, Hickman JA (1996) Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high bax:bcl-2 ratio. Cancer Res 56:1834-1841
162. 162. Masters JRW, Osborne EJ, Walker MC, Parris CN (1993) Hypersensitivity of human testis-tumour cell lines to chemotherapeutic drugs. Int J Cancer 53:340-346
163. 163. Hasegawa M, Zhang Y, Niibe H, Terry NH, Meistrich ML (1998) Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice. Radiat Res 149:263-270
164. 164. Socher SA, Yin Y, Dewolf WC, Morgentaler A (1997) Temperature-mediated germ cell loss in the testis is associated with altered expression of the cell-cycle regulator p53. J Urol 157:1986-1989
165. 165. Oliver RT (1996) Testicular cancer. Curr Opin Oncol 8: 252-258
166. 166. Oliver RT (1997) Testicular cancer. Curr Opin Oncol 9: 287-294
167. 167. Zambie DR, Jacks T, Lippard SJ (1998) p53-dependent and -independent responses to cisplatin in mouse testicular teratocarcinoma cells. Proc Natl Acad Sci USA 95: 6163-6168
168. 168. Lutzker SG, Levine AJ (1996) A functionally inactive p53 protein in teratocarcinoma cells is activated by either DNA damage or cellular differentiation. Nat Med 2:804-810
169. 169. Gersten KM, Kemp CJ (1997) Normal meiotic recombination in p53-deficient mice. Nat Genet 17:378-379
170. 170. Odorisio T, Rodriguez TA, Evans ER, Clarke AR, Burgoyne PS (1998) The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53 independent apoptosis. Nat Genet 18:257-261
171. 171. Keegan KS, Holtzman DA, Plug AW, Christenson ER, Brainerd EE, Flaggs G, Bentley NJ, Taylor EM, Meyn MS, Moss SR, Carr AM, Ashley T, Hoekstra MF (1996) The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes. Genes Dev 10:2423-2437
172. 172. Schwartz D, Goldfinger N, Karn Z, Rotter V (Submitted) p53 controls low DNA-damage-dependent premeiotic checkpoint and facilitates DNA repair during spermatogenesis.