The role of the cyclin-dependent kinase inhibitor p21 in apoptosis

Molecular Cancer Therapeutics

Volumn 1, Issue 8, 2002, Pages 639-649

  Gartel, Andrei L ^a   Tyner, Angela L ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CDKN1A PROTEIN, HUMAN; CDKN1A PROTEIN, MOUSE; CYCLIN DEPENDENT KINASE INHIBITOR 1A; CYCLINE; PROTEIN P53;

ANIMAL; APOPTOSIS; BIOLOGICAL MODEL; CELL DEATH; HUMAN; METABOLISM; MOUSE; NEOPLASM; PATHOLOGY; PHYSIOLOGY; REVIEW;

ANIMALS; APOPTOSIS; CELL DEATH; CYCLIN-DEPENDENT KINASE INHIBITOR P21; CYCLINS; HUMANS; MICE; MODELS, BIOLOGICAL; NEOPLASMS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 0036594890     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: None     Document Type: Review

References (173)

1. Sherr, C. J. Mammalian G1 cyclins. Cell, 73: 1059-1065, 1993.
2. Morgan, D. O. Principles of CDK regulation. Nature (Lond.), 374: 131-134, 1995.
3. Ekholm, S. V., and Reed, S. I. Regulation of G1 cyclin-dependent kinases in the mammalian cell cycle. Curr. Opin. Cell Biol., 12: 676-684, 2000.
4. Sherr, C. J., and Roberts, J. M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev., 13: 1501-1512, 1999. (Pubitemid 29297917)
5. Sherr, C. J. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res., 60: 3689-3695, 2000. (Pubitemid 32204552)
6. El-Deiry, W., Tokino, T., Velculescu, V., Levy, D., Parsons, R., Trent, J., Lin, D., Mercer, W. E., Kinzler, K., and Vogelstein, B. WAF1, a potential mediator of p53 tumor suppression. Cell, 75: 817-825, 1993. (Pubitemid 23346378)
7. Harper, J. W., Adami, G., Wei, N., Keyomarsi, K., and Elledge, S. The p21 cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell, 75: 805-816, 1993. (Pubitemid 23346377)
8. Xiong, Y., Hannon, G., Zhang, H., Casso, D., Kobayashi, R., and Beach, D. p21 is a universal inhibitor of cyclin kinases. Nature (Lond.), 366: 701-704, 1993. (Pubitemid 24036020)
9. Noda, A., Ning, Y., Venable, S. F., Pereira-Smith, O. M., and Smith, J. R. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell Res., 211: 90-98, 1994. (Pubitemid 24167339)
10. Polyak, K., Kato, J. Y., Solomon, M. J., Sherr, C. J., Massagué, J., Roberts, J. M., and Koff, A. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-β and contact inhibition to cell cycle arrest. Genes Dev., 8: 9-22, 1994.
11. Toyoshima, H., and Hunter, T. p27, a novel inhibitor of G1 cyclin/cdk protein kinase activity, is related to p21. Cell, 78: 67-74, 1994. (Pubitemid 24228301)
12. Lee, M. H., Reynisdottir, I., and Massagué, J. Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev., 9: 639-649, 1995.
13. Matsuoka, S., Edwards, M., Bai, C., Parker, S., Zhang, P., Baldini, A., Harper, J., and Elledge, S. p57, a structurally distinct member of the p21 cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev., 9: 650-662, 1995.
14. Polyak, K., Lee, M. H., Erdjument-Bromage, H., Koff, A., Roberts, J. M., Tempst, P., and Massagué, J. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular anti-mitogenic signals. Cell, 78: 59-66, 1994.
15. Chen, J., Jackson, P. K., Kirschner, M. W., and Dutta, A. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature (Lond.), 374: 386-388, 1995.
16. Luo, Y., Hurwitz, J., and Massagué, J. Cell-cycle inhibition by independent CDK and PCNA binding domains in p21. Nature (Lond.), 375: 159-161, 1995.
17. Harper, J. W., Elledge, S. J., Keyomarsi, K., Dynlacht, B., Tsai, L., Zhang, P., Dobtowolski, S., Bai, C., Connell-Crowley, L., Swindell, E., Fox, M. P., and Wei, N. Inhibition of cyclin dependent kinases by p21. Mol. Biol. Cell, 6: 387-400, 1995.
18. Zhang, H., Xiong, Y., and Beach, D. Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol. Biol. Cell, 4: 897-906, 1993. (Pubitemid 23309425)
19. Dulic, V., Kaufman, W. K., Wilson, S. J., Tlsty, T. D., Lees, E., Harper, J. W., Elledge, S. J., and Reed, S. I. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell, 76: 1013-1023, 1994. (Pubitemid 24106382)
20. Deng, C., Zhang, P., Harper, J. W., Elledge, S. J., and Leder, P. Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell, 82: 675-684, 1995.
21. Brugarolas, J., Chadrasekaran, C., Gordon, J., Beach, D., Jacks, T., and Hannon, G. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature (Lond.), 377: 552-557, 1995.
22. Niculescu, A. R., Chen, X., Smeets, M., Hengst, L., Prives, C., and Reed, S. I. Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication [published erratum appears in Mol. Cell. Biol., 18: 1763, 1998]. Mol. Cell. Biol., 18: 629-643, 1998. (Pubitemid 28021073)
23. Ogryzko, V. V., Wong, P., and Howard, B. H. WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent kinases. Mol. Cell. Biol., 17: 4877-4882, 1997. (Pubitemid 27318163)
24. Zhang, H., Hannon, G., and Beach, D. p21-containing cyclin kinases exist in both active and inactive states. Genes Dev., 8: 1750-1758, 1994.
25. Soos, T. J., Kiyokawa, H., Yan, J. S., Rubin, M. S., Giordano, A., DeBlasio, A., Bottega, S., Wong, B., Mendelsohn, J., and Koff, A. Formation of p27-CDK complexes during the human mitotic cell cycle. Cell Growth Differ., 7: 135-146, 1996. (Pubitemid 26049822)
26. Blain, S. W., Montalvo, E., and Massagué, J. Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4. J. Biol. Chem., 272: 25863-25872, 1997. (Pubitemid 27438911)
27. LaBaer, J., Garrett, M. D., Stevenson, L. F., Slingerland, J. M., Sandhu, C., Chou, H. S., Fattaey, A., and Harlow, E. New functional activities for the p21 family of CDK inhibitors. Genes Dev., 11: 847-862, 1997. (Pubitemid 27175292)
28. Besson, A., and Yong, V. W. Involvement of p21(Waf1/Cip1) in protein kinase Cα-induced cell cycle progression. Mol. Cell. Biol., 20: 4580-4590, 2000. (Pubitemid 30396106)
29. Weiss, R. H., Joo, A., and Randour, C. p21(Waf1/Cip1) is an assembly factor required for platelet-derived growth factor-induced vascular smooth muscle cell proliferation. J. Biol. Chem., 275: 10285-10290, 2000. (Pubitemid 30202086)
30. Cheng, M., Olivier, P., Diehl, J. A., Fero, M., Roussel, M. F., Roberts, J. M., and Sherr, C. J. The p21(Cip1) and p27(Kip1) CDK "inhibitors" are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J., 18: 1571-1583, 1999. (Pubitemid 29127070)
31. Bagui, T. K., Jackson, R. J., Agrawal, D., and Pledger, W. J. Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1). Mol. Cell. Biol., 20: 8748-8757, 2000. (Pubitemid 32245908)
32. Cheng, M., Sexl, V., Sherr, C. J., and Roussel, M. F. Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1). Proc. Natl. Acad. Sci. USA, 95: 1091-1096, 1998.
33. Perez-Roger, I., Kim, S. H., Griffiths, B., Sewing, A., and Land, H. Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1). EMBO J., 18: 5310-5320, 1999. (Pubitemid 29465581)
34. Bouchard, C., Thieke, K., Maier, A., Saffrich, R., Hanley-Hyde, J., Ansorge, W., Reed, S., Sicinski, P., Bartek, J., and Eilers, M. Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27. EMBO J., 18: 5321-5333, 1999. (Pubitemid 29465582)
35. McConnell, B. B., Gregory, F. J., Stott, F. J., Hara, E., and Peters, G. Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. Mol. Cell. Biol., 19: 1981-1989, 1999. (Pubitemid 29098256)
36. Tong, W., and Pollard, J. W. Genetic evidence for the interactions of cyclin D1 and p27(Kip1) in mice. Mol. Cell. Biol., 21: 1319-1328, 2001. (Pubitemid 32114979)
37. Geng, Y., Yu, Q., Sicinska, E., Das, M., Bronson, R. T., and Sicinski, P. Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice. Proc. Natl. Acad. Sci. USA, 98: 194-199, 2001. (Pubitemid 32095886)
38. Tsutsui, T., Hesabi, B., Moons, D. S., Pandolfi, P. P., Hansel, K. S., Koff, A., and Kiyokawa, H. Targeted disruption of CDK4 delays cell cycle entry with enhanced p27(Kip1) activity. Mol. Cell. Biol., 19: 7011-7019, 1999. (Pubitemid 29441883)
39. Xiong, Y., Zhang, H., and Beach, D. D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell, 71: 505-514, 1992.
40. Tsurimoto, T. PCNA binding proteins. Front. Biosci., 4: D849-D858, 1999.
41. Warbrick, E. The puzzle of PCNA's many partners. Bioessays, 22: 997-1006, 2000.
42. Waga, S., Hannon, G., Beach, D., and Stillman, B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature (Lond.), 369: 574-578, 1994. (Pubitemid 24192528)
43. Flores-Rozas, H., Kelman, Z., Dean, F. B., Pan, Z. Q., Harper, J. W., Elledge, S. J., O'Donnell, M. O., and Hurwitz, J. Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymer as delta holoenzyme. Proc. Natl. Acad. Sci. USA, 91: 8655-8659, 1994. (Pubitemid 24273723)
44. Gibbs, E., Kelman, Z., Gulbis, J. M., O'Donnell, M., Kuriyan, J., Burgers, P., and Hurwitz, J. The influence of the proliferating cell nuclear antigen-interacting domain of p21(CIP1) on DNA synthesis catalyzed by the human and Saccharomyces cerevisiae polymerase delta holoenzymes. J. Biol. Chem., 272: 2373-2381, 1997. (Pubitemid 27058525)
45. McDonald, E. R., Wu, G. S., Waldman, T., and El-Deiry, W. S. Repair defect in p21 WAF1/CIP1 -/- human cancer cells. Cancer Res., 56: 2250-2255, 1996.
46. Sheikh, M. S., Chen, Y. Q., Smith, M. L., and Fornace, A. J., Jr. Role of p21Waf1/Cip1/Sdi1 in cell death and DNA repair as studied using a tetracycline-inducible system in p53-deficient cells. Oncogene, 14: 1875-1882, 1997. (Pubitemid 27207689)
47. Li, R., Waga, S., Hannon, G., Beach, D., and Stillman, B. Differential effects by the p21 CDK inhibitor on PCNA dependent DNA replication and repair. Nature, 371: 534-537, 1994. (Pubitemid 24306614)
48. Shivji, M. K., Grey, S. J., Strausfeld, U. P., Wood, R. D., and Blow, J. J. Cip1 inhibits DNA replication but not PCNA-dependent nucleotide excision-repair. Curr. Biol., 4: 1062-1068, 1994. (Pubitemid 124001592)
49. Adimoolam, S., Lin, C. X., and Ford, J. M. The p53-regulated cyclin-dependent kinase inhibitor, p21 (cip1, waf1, sdi1), is not required for global genomic and transcription-coupled nucleotide excision repair of UV-induced DNA photoproducts. J. Biol. Chem., 276: 25813-25822, 2001.
50. Pan, Z. Q., Reardon, J. T., Li, L., Flores-Rozas, H., Legerski, R., Sancar, A., and Hurwitz, J. Inhibition of nucleotide excision repair by the cyclin-dependent kinase inhibitor p21. J. Biol. Chem., 270: 22008-22016, 1995.
51. Cooper, M. P., Balajee, A. S., and Bohr, V. A. The C-terminal domain of p21 inhibits nucleotide excision repair in vitro and in vivo. Mol. Biol. Cell, 10: 2119-2129, 1999. (Pubitemid 29343123)
52. Umar, A., Buermeyer, A. B., Simon, J. A., Thomas, D. C., Clark, A. B., Liskay, R. M., and Kunkel, T. A. Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell, 87: 65-73, 1996. (Pubitemid 26337391)
53. Tom, S., Ranalli, T. A., Podust, V. N., and Bambara, R. A. Regulatory roles of p21 and apurinic/apyrimidinic endonuclease 1 in base excision repair. J. Biol. Chem., 276: 48781-48789, 2001.
54. Gartel, A. L., and Tyner, A. L. Transcriptional regulation of the p21(WAF1/CIP1) gene. Exp. Cell Res., 246: 280-289, 1999.
55. El-Deiry, W. S., Tokino, T., Waldman, T., Oliner, J. D., Velculscu, V. E., Burrel, M., Hill, D. E., Healy, E., Rees, J. L., Hamilton, S. R., Kinzler, K. W., and Vogelstein, B. Topological control of p21 (WAF1/CIP1) expression in normal and neoplastic tissues. Cancer Res., 55: 2910-2919, 1995.
56. Maki, C. G., and Howley, P. M. Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation. Mol. Cell. Biol., 17: 355-363, 1997. (Pubitemid 26425625)
57. Sheaff, R. J., Singer, J. D., Swanger, J., Smitherman, M., Roberts, J. M., and Clurman, B. E. Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination. Mol. Cell, 5: 403-410, 2000. (Pubitemid 30628097)
58. Touitou, R., Richardson, J., Bose, S., Nakanishi, M., Rivett, J., and Allday, M. J. A degradation signal located in the C-terminus of p21WAF1/CIP1 is a binding site for the C8α subunit of the 20S proteasome. EMBO J., 20: 2367-2375, 2001. (Pubitemid 32452854)
59. Parker, S., Eichele, G., Zhang, P., Rawls, A., Sands, A., Bradley, A., Olson, E., Harper, J., and Elledge, S. p53-independent expression of p21 in muscle and other terminally differentiating cells. Science (Wash. DC), 267: 1024-1027, 1995.
60. Macleod, K., Sherry, N., Hannon, G., Beach, D., Tokino, T., Kinzler, K., Vogelstein, B., and Jacks, T. p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev., 9: 935-944, 1995.
61. Huppi, K., Siwarski, D., Dosik, J., Michieli, P., Chedid, M., Reed, S., Mock, B., Givol, D., and Mushinski, J. F. Molecular cloning, sequencing, chromosomal location and expression of mouse p21 (Waf1). Oncogene, 9: 3017-3020, 1994. (Pubitemid 24296779)
62. Gartel, A. L., Serfas, M. S., Gartel, M., Goufman, E., Wu, G. S., el-Deiry, W. S., and Tyner, A. L. p21 (WAF1/CIP1) expression is induced in newly nondividing cells in diverse epithelia and during differentiation of the Caco-2 intestinal cell line. Exp. Cell Res., 227: 171-181, 1996. (Pubitemid 26320157)
63. Brown, J. P., Wei, W., and Sedivy, J. M. Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science (Wash. DC), 277: 831-834, 1997. (Pubitemid 27366737)
64. Chang, B. D., Watanabe, K., Broude, E. V., Fang, J., Poole, J. C., Kalinichenko, T. V., and Roninson, I. B. Effects of p21Waf1/Cip1/Sdi1 on cellular gene expression: implications for carcinogenesis, senescence, and age-related diseases. Proc. Natl. Acad. Sci. USA, 97: 4291-4296, 2000. (Pubitemid 30226126)
65. Topley, G. I., Okuyama, R., Gonzales, J. G., Conti, C., and Dotto, G. P. p21(WAF1/Cip1) functions as a suppressor of malignant skin tumor formation and a determinant of keratinocyte stem-cell potential. Proc. Natl. Acad. Sci. USA, 96: 9089-9094, 1999. (Pubitemid 29374712)
66. Cheng, T., Rodrigues, N., Shen, H., Yang, Y., Dombkowski, D., Sykes, M., and Scadden, D. T. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science (Wash. DC), 287: 1804-1808, 2000.
67. Balomenos, D., Martin-Caballero, J., Garcia, M. I., Prieto, I., Flores, J. M., Serrano, M., and Martinez, A. C. The cell cycle inhibitor p21 controls T-cell proliferation and sex-linked lupus development. Nat. Med., 6: 171-176, 2000. (Pubitemid 30082361)
68. Megyesi, J., Price, P. M., Tamayo, E., and Safirstein, R. L. The lack of a functional p21(WAF1/CIP1) gene ameliorates progression to chronic renal failure. Proc. Natl. Acad. Sci. USA, 96: 10830-10835, 1999. (Pubitemid 29442229)
69. Halevy, O., Novitch, B. G., Spicer, D. B., Skapek, S. X., Rhee, J., Hannon, G. J., Beach, D., and Lassar, A. B. Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science (Wash. DC), 267: 1018-1021, 1995.
70. Zhang, P., Wong, C., Liu, D., Finegold, M., Harper, J. W., and Elledge, S. J. p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step. Genes Dev., 13: 213-224, 1999. (Pubitemid 29061951)
71. Martin-Caballero, J., Flores, J. M., Garcia-Palencia, P., and Serrano, M. Tumor susceptibility of p21(Waf1/Cip1)-deficient mice. Cancer Res., 61: 6234-6238, 2001.
72. Franklin, D. S., Godfrey, V. L., O'Brien, D. A., Deng, C., and Xiong, Y. Functional collaboration between different cyclin-dependent kinase inhibitors suppresses tumor growth with distinct tissue specificity. Mol. Cell. Biol., 20: 6147-6158, 2000. (Pubitemid 30613062)
73. Philipp, J., Vo, K., Gurley, K. E., Seidel, K., and Kemp, C. J. Tumor suppression by p27Kip1 and p21Cip1 during chemically induced skin carcinogenesis. Oncogene, 18: 4689-4698, 1999. (Pubitemid 29417744)
74. Adnane, J., Jackson, R. J., Nicosia, S. V., Cantor, A. B., Pledger, W. J., and Sebti, S. M. Loss of p21WAF1/CIP1 accelerates Ras oncogenesis in a transgenic/knockout mammary cancer model. Oncogene, 19: 5338-5347, 2000.
75. Brugarolas, J., Bronson, R. T., and Jacks, T. p21 is a critical CDK2 regulator essential for proliferation control in Rb-deficient cells. J. Cell Biol., 141: 503-514, 1998. (Pubitemid 28237097)
76. Paramio, J. M., Segrelles, C., Ruiz, S., Martin-Caballero, J., Page, A., Martinez, J., Serrano, M., and Jorcano, J. L. The ink4a/arf tumor suppressors cooperate with p21cip1/waf in the processes of mouse epidermal differentiation, senescence, and carcinogenesis. J. Biol. Chem., 276: 44203-44211, 2001.
77. Attardi, L. D., Lowe, S. W., Brugarolas, J., and Jacks, T. Transcriptional activation by p53, but not induction of the p21 gene, is essential for oncogene-mediated apoptosis. EMBO J., 15: 3693-3701, 1996. (Pubitemid 26239782)
78. Zhang, Y., Fujita, N., and Tsuruo, T. Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. Oncogene, 18: 1131-1138, 1999. (Pubitemid 29085985)
79. Kaneuchi, M., Yamashita, T., Shindoh, M., Segawa, K., Takahashi, S., Furuta, I., Fujimoto, S., and Fujinaga, K. Induction of apoptosis by the p53-273L (Arg→Leu) mutant in HSC3 cells without transactivation of p21Waf1/Cip1/Sdi1 and bax. Mol. Carcinog., 26: 44-52, 1999. (Pubitemid 29420185)
80. Okaichi, K., Wang, L. H., Sasaki, J., Saya, H., Tada, M., and Okumura, Y. A point mutation of human p53, which was not detected as a mutation by a yeast functional assay, led to apoptosis but not p21Waf1/Cip1/Sdi1 expression in response to ionizing radiation in a human osteosarcoma cell line, Saos-2. Int. J. Radiat. Oncol. Biol. Phys., 45: 975-980, 1999. (Pubitemid 29525462)
81. Kokontis, J. M., Wagner, A. J., O'Leary, M., Liao, S., and Hay, N. A transcriptional activation function of p53 is dispensable for and inhibitory of its apoptotic function. Oncogene, 20: 659-668, 2001. (Pubitemid 32179334)
82. Bissonnette, N., and Hunting, D. J. p21-induced cycle arrest in G1 protects cells from apoptosis induced by UV-irradiation or RNA polymerase II blockage. Oncogene, 16: 3461-3469, 1998. (Pubitemid 28349689)
83. Chang, W. T., Kang, J. J., Lee, K. Y., Wei, K., Anderson, E., Gotmare, S., Ross, J. A., and Rosen, G. D. Triptolide and chemotherapy cooperate in tumor cell apoptosis. A role for the p53 pathway. J. Biol. Chem., 276: 2221-2227, 2001. (Pubitemid 32109705)
84. Samuels-Lev, Y., O'Connor, D. J., Bergamaschi, D., Trigiante, G., Hsieh, J. K., Zhong, S., Campargue, I., Naumovski, L., Crook, T., and Lu, X. ASPP proteins specifically stimulate the apoptotic function of p53. Mol. Cell, 8: 781-794, 2001. (Pubitemid 33030212)
85. Shaulian, E., Schreiber, M., Piu, F., Beeche, M., Wagner, E. F., and Karin, M. The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest. Cell, 103: 897-907, 2000.
86. Bunz, F., Hwang, P. M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K. W., and Vogelstein, B. Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J. Clin. Investig., 104: 263-269, 1999.
87. Chan, T. A., Hwang, P. M., Hermeking, H., Kinzler, K. W., and Vogelstein, B. Cooperative effects of genes controlling the G(2)/M checkpoint. Genes Dev., 14: 1584-1588, 2000. (Pubitemid 30460907)
88. Chattopadhyay, D., Ghosh, M. K., Mal, A., and Harter, M. L. Inactivation of p21 by E1A leads to the induction of apoptosis in DNA- damaged cells. J. Virol., 75: 9844-9856, 2001. (Pubitemid 32900120)
89. Lu, Y., Tatsuka, M., Takebe, H., and Yagi, T. Involvement of cyclin-dependent kinases in doxorubicin-induced apoptosis in human tumor cells. Mol. Carcinog., 29: 1-7, 2000.
90. Prabhu, N. S., Somasundaram, K., Tian, H., Enders, G. H., Satyamoorthy, K., Herlyn, M., and El-Deiry, W. S. The administration schedule of cyclin-dependent kinase inhibitor gene therapy and etoposide chemotherapy is a major determinant of cytotoxicity. Int. J. Oncol., 15: 209-216, 1999.
91. Canman, C. E., Gilmer, T. M., Coutts, S. B., and Kastan, M. B. Growth factor modulation of p53-mediated growth arrest versus apoptosis. Genes Dev., 9: 600-611, 1995.
92. Waldman, T., Zhang, Y., Dillehay, L., Yu, J., Kinzler, K., Vogelstein, B., and Williams, J. Cell-cycle arrest versus cell death in cancer therapy. Nat. Med., 3: 1034-1036, 1997. (Pubitemid 27391962)
93. Tian, H., Wittmack, E. K., and Jorgensen, T. J. p21WAF1/CIP1 anti-sense therapy radiosensitizes human colon cancer by converting growth arrest to apoptosis. Cancer Res., 60: 679-684, 2000. (Pubitemid 30094567)
94. Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., and Pelicci, P. G. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature (Lond.), 402: 309-313, 1999. (Pubitemid 129516269)
95. Yang, F., von Knethen, A., and Brune, B. Modulation of nitric oxide-evoked apoptosis by the p53-downstream target p21(WAF1/CIP1). J. Leukocyte Biol., 68: 916-922, 2000.
96. Bauer, P. M., Buga, G. M., and Ignarro, L. J. Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide. Proc. Natl. Acad. Sci. USA, 98: 12802-12807, 2001. (Pubitemid 33020025)
97. Helt, C. E., Rancourt, R. C., Staversky, R. J., and O'Reilly, M. A. p53-dependent induction of p21(Cip1/WAF1/Sdi1) protects against oxygen-induced toxicity. Toxicol. Sci., 63: 214-222, 2001. (Pubitemid 32982795)
98. Polyak, K., Waldman, T., He, T. C., Kinzler, K. W., and Vogelstein, B. Genetic determinants of p53-induced apoptosis and growth arrest. Genes Dev., 10: 1945-1952, 1996. (Pubitemid 26281688)
99. Gorospe, M., Cirielli, C., Wang, X., Seth, P., Capogrossi, M., and Holbrook, N. P21 (WAF1/CIP1) protects against p53-mediated apoptosis of human melanoma cells. Oncogene, 14: 929-935, 1997. (Pubitemid 27122425)
100. Kim, D. K., Cho, E. S., Lee, S. J., and Um, H. D. Constitutive hyperexpression of p21(WAF1) in human U266 myeloma cells blocks the lethal signaling induced by oxidative stress but not by Fas. Biochem. Biophys. Res. Commun., 289: 34-38, 2001.
101. Yan, Q., and Sage, E. H. Transforming growth factor-β1 induces apoptotic cell death in cultured retinal endothelial cells but not pericytes: association with decreased expression of p21waf1/cip1. J. Cell. Biochem., 70: 70-83, 1998. (Pubitemid 28310921)
102. Javelaud, D., Wietzerbin, J., Delattre, O., and Besancon, F. Induction of p21Waf1/Cip1 by TNFα requires NF-κB activity and antagonizes apoptosis in Ewing tumor cells. Oncogene, 19: 61-68, 2000. (Pubitemid 30066351)
103. Zhu, J., Jiang, J., Zhou, W., and Chen, X. The potential tumor suppressor p73 differentially regulates cellular p53 target genes. Cancer Res., 58: 5061-5065, 1998. (Pubitemid 28521161)
104. Pennington, K. N., Taylor, J. A., Bren, G. D., and Paya, C. V. IκB kinase-dependent chronic activation of NF-κB is necessary for p21(WAF1/Cip1) inhibition of differentiation-induced apoptosis of monocytes. Mol. Cell. Biol., 21: 1930-1941, 2001. (Pubitemid 32479617)
105. Donato, N. J., and Perez, M. Tumor necrosis factor-induced apoptosis stimulates p53 accumulation and p21WAF1 proteolysis in ME-180 cells. J. Biol. Chem., 273: 5067-5072, 1998. (Pubitemid 28108665)
106. Glaser, T., Wagenknecht, B., and Weller, M. Identification of p21 as a target of cycloheximide-mediated facilitation of CD95-mediated apoptosis in human malignant glioma cells. Oncogene, 20: 4757-4767, 2001. (Pubitemid 32803147)
107. Hobeika, A. C., Etienne, W., Torres, B. A., Johnson, H. M., and Subramaniam, P. S. IFN-γ induction of p21(WAF1) is required for cell cycle inhibition and suppression of apoptosis. J. Interferon Cytokine Res., 19: 1351-1361, 1999. (Pubitemid 30032937)
108. Xaus, J., Cardo, M., Valledor, A. F., Soler, C., Lloberas, J., and Celada, A. Interferon γ induces the expression of p21waf-1 and arrests macrophage cell cycle, preventing induction of apoptosis. Immunity, 11: 103-113, 1999. (Pubitemid 29359961)
109. Xaus, J., Comalada, M., Cardo, M., Valledor, A. F., and Celada, A. Decorin inhibits macrophage colony-stimulating factor proliferation of macrophages and enhances cell survival through induction of p27(Kip1) and p21(Waf1). Blood, 98: 2124-2133, 2001.
110. Bellido, T., O'Brien, C. A., Roberson, P. K., and Manolagas, S. C. Transcriptional activation of the p21(WAF1, CIP1, SDI1) gene by interleukin-6 type cytokines. A prerequisite for their pro-differentiating and antiapoptotic effects on human osteoblastic cells. J. Biol. Chem., 273: 21137-21144, 1998. (Pubitemid 28385402)
111. Suzuki, T., Yokozaki, H., Kuniyasu, H., Hayashi, K., Naka, K., Ono, S., Ishikawa, T., Tahara, E., and Yasui, W. Effect of trichostatin A on cell growth and expression of cell cycle- and apoptosis-related molecules in human gastric and oral carcinoma cell lines. Int. J. Cancer, 88: 992-997, 2000.
112. Chai, F., Evdokiou, A., Young, G. P., and Zalewski, P. D. Involvement of p21(Waf1/Cip1) and its cleavage by DEVD-caspase during apoptosis of colorectal cancer cells induced by butyrate. Carcinogenesis (Lond.), 21: 7-14, 2000. (Pubitemid 30064137)
113. Mahyar-Roemer, M., and Roemer, K. p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agents. Oncogene, 20: 3387-3398, 2001. (Pubitemid 32588987)
114. Vrana, J. A., Decker, R. H., Johnson, C. R., Wang, Z., Jarvis, W. D., Richon, V. M., Ehinger, M., Fisher, P. B., and Grant, S. Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53. Oncogene, 18: 7016-7025, 1999. (Pubitemid 30028872)
115. Burgess, A. J., Pavey, S., Warrener, R., Hunter, L. J., Piva, T. J., Musgrove, E. A., Saunders, N., Parsons, P. G., and Gabrielli, B. G. Upregulation of p21(WAF1/CIP1) by histone deacetylase inhibitors reduces their cytotoxicity. Mol. Pharmacol., 60: 828-837, 2001. (Pubitemid 32900266)
116. Gorospe, M., Wang, X., Guyton, K., and Holbrook, N. Protective role of p21 (WAF1/CIP1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells. Mol. Cell. Biol., 16: 6654-6660, 1996. (Pubitemid 26389723)
117. Hitomi, M., Shu, J., Strom, D., Hiebert, S. W., Harter, M. L., and Stacey, D. W. Prostaglandin A2 blocks the activation of G1 phase cyclin-dependent kinase without altering mitogen-activated protein kinase stimulation. J. Biol. Chem., 271: 9376-9383, 1996. (Pubitemid 26137344)
118. Gorospe, M., Shack, S., Guyton, K., Samid, D., and Holbrook, N. Up-regulation and functional role of p21 (WAF1/CIP1) during growth arrest of human breast carcinoma MCF-7 cells by phenylacetate. Cell Growth Differ., 7: 1609-1615, 1996. (Pubitemid 26415156)
119. Ruan, S., Okcu, M. F., Ren, J. P., Chiao, P., Andreeff, M., Levin, V., and Zhang, W. Overexpressed WAF1/Cip1 renders glioblastoma cells resistant to chemotherapy agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Cancer Res., 58: 1538-1543, 1998. (Pubitemid 28193621)
120. Wang, Y., Blandino, G., and Givol, D. Induced p21waf expression in H1299 cell line promotes cell senescence and protects against cytotoxic effect of radiation and doxorubicin. Oncogene, 18: 2643-2649, 1999. (Pubitemid 29216687)
121. Xu, G. W., Nutt, C. L., Zlatescu, M. C., Keeney, M., Chin-Yee, I., and Cairncross, J. G. Inactivation of p53 sensitizes U87MG glioma cells to 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res., 61: 4155-4159, 2001. (Pubitemid 32720984)
122. 2/M arrest and inhibits apoptosis. Carcinogenesis (Lond.), 21: 1941-1945, 2000.
123. Wang, Z., Van Tuyle, G., Conrad, D., Fisher, P. B., Dent, P., and Grant, S. Dysregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/MDA6 increases the susceptibility of human leukemia cells (U937) to 1-β-D-arabinofuranosylcytosine-mediated mitochondrial dysfunction and apoptosis. Cancer Res., 59: 1259-1267, 1999. (Pubitemid 29136256)
124. Wang, Y. A., Elson, A., and Leder, P. 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, 1997. (Pubitemid 28041418)
125. Marches, R., Hsueh, R., and Uhr, J. W. Cancer dormancy and cell signaling: induction of p21(waf1) initiated by membrane IgM engagement increases survival of B lymphoma cells. Proc. Natl. Acad. Sci. USA, 96: 8711-8715, 1999. (Pubitemid 29354856)
126. Wouters, B. G., Giaccia, A. J., Denko, N. C., and Brown, J. M. Loss of p21Waf1/Cip1 sensitizes tumors to radiation by an apoptosis-independent mechanism. Cancer Res., 57: 4703-4706, 1997. (Pubitemid 27468970)
127. Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., and McGuire, W. L. Human breast cancer: correlation and relapse and survival with amplification of the HER-2/neu oncogene. Science (Wash. DC), 235: 177-182, 1987. (Pubitemid 17231334)
128. Yu, D., Liu, B., Tan, M., Li, J., Wang, S. S., and Hung, M. C. Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. Oncogene, 13: 1359-1365, 1996. (Pubitemid 26343590)
129. Horwitz, S. B. Mechanism of action of Taxol. Trends Pharmacol. Sci., 13: 134-136, 1992.
130. Linke, S. P., Clarkin, K. C., Di Leonardo, A., Tsou, A., and Wahl, G. M. A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev., 10: 934-947, 1996. (Pubitemid 26138705)
131. Stewart, Z. A., Mays, D., and Pietenpol, J. A. Defective G1-S cell cycle checkpoint function sensitizes cells to microtubule inhibitor-induced apoptosis. Cancer Res., 59: 3831-3837, 1999. (Pubitemid 29381893)
132. Li, W., Fan, J., Banerjee, D., and Bertino, J. R. Overexpression of p21(waf1) decreases G2-M arrest and apoptosis induced by paclitaxel in human sarcoma cells lacking both p53 and functional Rb protein. Mol. Pharmacol., 55: 1088-1093, 1999. (Pubitemid 29252376)
133. Schmidt, M., Lu, Y., Liu, B., Fang, M., Mendelsohn, J., and Fan, Z. Differential modulation of paclitaxel-mediated apoptosis by p21Waf1 and p27Kip1. Oncogene, 19: 2423-2429, 2000. (Pubitemid 30323475)
134. Zhou, B. P., Liao, Y., Xia, W., Spohn, B., Lee, M. H., and Hung, M. C. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat. Cell Biol., 3: 245-252, 2001. (Pubitemid 32201319)
135. Asada, M., Yamada, T., Ichijo, H., Delia, D., Miyazono, K., Fukumuro, K., and Mizutani, S. Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation. EMBO J., 18: 1223-1234, 1999. (Pubitemid 29110307)
136. Yu, D., Jing, T., Liu, B., Yao, J., Tan, M., McDonnell, T. J., and Hung, M. C. Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol. Cell, 2: 581-591, 1998. (Pubitemid 128379084)
137. Li, Y., Dowbenko, D., and Lasky, L. A. AKT/PKB phosphorylation of p21Cip1/WAF1 enhances protein stability of p21Cip1/WAF1 and promotes cell survival. J. Biol. Chem., 277: 11352-11361, 2002. (Pubitemid 34952901)
138. Lawlor, M. A., and Rotwein, P. Insulin-like growth factor-mediated muscle cell survival: central roles for Akt and cyclin-dependent kinase inhibitor p21. Mol. Cell. Biol., 20: 8983-8995, 2000. (Pubitemid 32245928)
139. Wang, J., and Walsh, K. Resistance to apoptosis conferred by cdk inhibitors during myocyte differentiation. Science (Wash. DC), 273: 359-361, 1996. (Pubitemid 26250264)
140. Fujio, Y., Guo, K., Mano, T., Mitsuuchi, Y., Testa, J. R., and Walsh, K. Cell cycle withdrawal promotes myogenic induction of Akt, a positive modulator of myocyte survival. Mol. Cell. Biol., 19: 5073-5082, 1999. (Pubitemid 29289545)
141. Poluha, W., Poluha, D. K., Chang, B., Crosbie, N. E., Schonhoff, C. M., Kilpatrick, D. L., and Ross, A. H. The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. Mol. Cell. Biol., 16: 1335-1341, 1996.
142. Raj, K., Ogston, P., and Beard, P. Virus-mediated killing of cells that lack p53 activity. Nature (Lond.), 412: 914-917, 2001. (Pubitemid 32821736)
143. Vogelstein, B., and Kinzler, K. W. Achilles' heel of cancer? Nature (Lond.), 412: 865-866, 2001. (Pubitemid 32821714)
144. Schmidt, M., and Fan, Z. Protection against chemotherapy-induced cytotoxicity by cyclin-dependent kinase inhibitors (CKI) in CKI-responsive cells compared with CKI-unresponsive cells. Oncogene, 20: 6164-6171, 2001. (Pubitemid 32964428)
145. Levkau, B., Koyama, H., Raines, E. W., Clurman, B. E., Herren, B., Orth, K., Roberts, J. M., and Ross, R. Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade. Mol. Cell, 1: 553-563, 1998. (Pubitemid 128374691)
146. Gervais, J. L., Seth, P., and Zhang, H. Cleavage of CDK inhibitor p21(Cip1/Waf1) by caspases is an early event during DNA damage-induced apoptosis. J. Biol. Chem., 273: 19207-19212, 1998. (Pubitemid 28366319)
147. Jin, Y. H., Yoo, K. J., Lee, Y. H., and Lee, S. K. Caspase 3-mediated cleavage of p21WAF1/CIP1 associated with the cyclin A-cyclin-dependent kinase 2 complex is a prerequisite for apoptosis in SK-HEP-1 cells. J. Biol. Chem., 275: 30256-30263, 2000.
148. Adachi, S., Ito, H., Tamamori-Adachi, M., Ono, Y., Nozato, T., Abe, S., Ikeda, M., Marumo, F., and Hiroe, M. Cyclin A/cdk2 activation is involved in hypoxia-induced apoptosis in cardiomyocytes. Circ. Res., 88: 408-414, 2001. (Pubitemid 32200114)
149. Harvey, K. J., Lukovic, D., and Ucker, D. S. Caspase-dependent Cdk activity is a requisite effector of apoptotic death events. J. Cell Biol., 148: 59-72, 2000. (Pubitemid 30046782)
150. de La Fuente, C., Santiago, F., Chong, S. Y., Deng, L., Mayhood, T., Fu, P., Stein, D., Denny, T., Coffman, F., Azimi, N., Mahieux, R., and Kashanchi, F. Overexpression of p21(waf1) in human T-cell lymphotropic virus type 1-infected cells and its association with cyclin A/cdk2. J. Virol., 74: 7270-7283, 2000. (Pubitemid 30613074)
151. Xu, S. Q., and El-Deiry, W. S. p21(WAF1/CIP1) inhibits initiator caspase cleavage by TRAIL death receptor DR4. Biochem. Biophys. Res. Commun., 269: 179-190, 2000. (Pubitemid 30440274)
152. Suzuki, A., Tsutomi, Y., Akahane, K., Araki, T., and Miura, M. Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP. Oncogene, 17: 931-939, 1998. (Pubitemid 28425403)
153. Steinman, R. A., and Johnson, D. E. p21WAF1 prevents downmodulation of the apoptotic inhibitor protein c-IAP1 and inhibits leukemic apoptosis. Mol. Med., 6: 736-749, 2000.
154. Suzuki, A., Tsutomi, Y., Miura, M., and Akahane, K. Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21. Oncogene, 18: 1239-1244, 1999. (Pubitemid 29085997)
155. Suzuki, A., Tsutomi, Y., Yamamoto, N., Shibutani, T., and Akahane, K. Mitochondrial regulation of cell death: mitochondria are essential for procaspase 3-p21 complex formation to resist Fas-mediated cell death. Mol. Cell. Biol., 19: 3842-3847, 1999. (Pubitemid 29193843)
156. Fotedar, R., Brickner, H., Saadatmandi, N., Rousselle, T., Diederich, L., Munshi, A., Jung, B., Reed, J. C., and Fotedar, A. Effect of p21waf1/cip1 transgene on radiation induced apoptosis in T cells. Oncogene, 18: 3652-3658, 1999. (Pubitemid 29322391)
157. Shibata, M. A., Yoshidome, K., Shibata, E., Jorcyk, C. L., and Green, J. E. Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21. Cancer Gene Ther., 8: 23-35, 2001. (Pubitemid 32151894)
158. Kondo, S., Barna, B. P., Kondo, Y., Tanaka, Y., Casey, G., Liu, J., Morimura, T., Kaakaji, R., Peterson, J. W., Werbel, B., and Barnett, G. H. WAF1/CIP1 increases the susceptibility of p53 non-functional malignant glioma cells to cisplatin-induced apoptosis. Oncogene, 13: 1279-1285, 1996. (Pubitemid 26343581)
159. Lincet, H., Poulain, L., Remy, J. S., Deslandes, E., Duigou, F., Gauduchon, P., and Staedel, C. The p21(cip1/waf1) cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells. Cancer Lett., 161: 17-26, 2000.
160. Kang, K. H., Kim, W. H., and Choi, K. H. p21 promotes ceramide-induced apoptosis and antagonizes the antideath effect of Bcl-2 in human hepatocarcinoma cells. Exp. Cell Res., 253: 403-412, 1999. (Pubitemid 30003101)
161. Hsu, S. L., Chen, M. C., Chou, Y. H., Hwang, G. Y., and Yin, S. C. Induction of p21(CIP1/Waf1) and activation of p34(cdc2) involved in retinoic acid-induced apoptosis in human hepatoma Hep3B cells. Exp. Cell. Res., 248: 87-96, 1999.
162. Li, Y., Upadhyay, S., Bhuiyan, M., and Sarkar, F. H. Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein. Oncogene, 18: 3166-3172, 1999. (Pubitemid 29261238)
163. Tsao, Y. P., Huang, S. J., Chang, J. L., Hsieh, J. T., Pong, R. C., and Chen, S. L. Adenovirus-mediated p21(WAF1/SDII/CIP1) gene transfer induces apoptosis of human cervical cancer cell lines. J. Virol., 73: 4983-4990, 1999.
164. Kadowaki, Y., Fujiwara, T., Fukazawa, T., Shao, J., Yasuda, T., Itoshima, T., Kagawa, S., Hudson, L. G., Roth, J. A., and Tanaka, N. Induction of differentiation-dependent apoptosis in human esophageal squamous cell carcinoma by adenovirus-mediated p21sdi1 gene transfer. Clin. Cancer Res., 5: 4233-4241, 1999. (Pubitemid 30013810)
165. Yang, Z. Y., Perkins, N. D., Ohno, T., Nabel, E. G., and Nabel, G. J. The p21 cyclin-dependent kinase inhibitor suppresses tumorigenicity in vivo. Nat. Med., 1: 1052-1056, 1995.
166. Hingorani, R., Bi, B., Dao, T., Bae, Y., Matsuzawa, A., and Crispe, I. N. CD95/Fas signaling in T lymphocytes induces the cell cycle control protein p21cip-1/WAF-1, which promotes apoptosis. J. Immunol., 164: 4032-4036, 2000. (Pubitemid 30215057)
167. Goke, R., Goke, A., Goke, B., El-Deiry, W. S., and Chen, Y. Pioglitazone inhibits growth of carcinoid cells and promotes TRAIL-induced apoptosis by induction of p21waf1/cip1. Digestion, 64: 75-80, 2001. (Pubitemid 34701873)
168. Shin, B. A., Ahn, K. Y., Kook, H., Koh, J. T., Kang, I. C., Lee, H. C., and Kim, K. K. Overexpressed human RAD50 exhibits cell death in a p21(WAF1/CIP1)-dependent manner: its potential utility in local gene therapy of tumor. Cell Growth Differ., 12: 243-254, 2001. (Pubitemid 32678227)
169. Chinery, R., Brockman, J., Peeler, M. O., Shyr, Y., Beauchamp, R. D., and Coffey, R. J. Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21 (WAF1/CIP1) via C/EBPβ. Nat. Med., 3: 1233-1241, 1997. (Pubitemid 27508824)
170. Bach, S. P., Chinery, R., O'Dwyer, S. T., Potten, C. S., Coffey, R. J., and Watson, A. J. Pyrrolidine dithiocarbamate increases the therapeutic index of 5-fluorouracil in a mouse model. Gastroenterology, 118: 81-89, 2000. (Pubitemid 30020375)
171. Ahmad, N., Adhami, V. M., Afaq, F., Feyes, D. K., and Mukhtar, H. Resveratrol causes WAF-1/p21-mediated G1-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells. Clin. Cancer Res., 7: 1466-1473, 2001. (Pubitemid 32708704)
172. Evan, G. I., and Vousden, K. H. Proliferation, cell cycle and apoptosis in cancer. Nature (Lond.), 411: 342-348, 2001. (Pubitemid 32467043)
173. Gartel, A. L., Serfas, M. S., and Tyner, A. L. p21-negative regulator of the cell cycle. Proc. Soc. Exp. Biol. Med., 213: 138-149, 1996.