Flavopiridol-Induced Apoptosis during S Phase Requires E2F-1 and Inhibition of Cyclin A-Dependent Kinase Activity

Cancer Research

Volumn 63, Issue 21, 2003, Pages 7410-7422

  Jiang, Jingrui ^a   Matranga, Christian B ^a,c   Cai, Dongpo ^a   Latham Jr , Vaughan M ^a   Zhang, Xinxin ^a   Lowell, April M ^a   Martelli, Fabio ^a,d   Shapiro, Geoffrey I ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^d LABORATORIO DI PATOLOGIA VASCOLARE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN A; CYCLIN A DEPENDENT KINASE; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE INHIBITOR; DNA; FLAVOPIRIDOL; GEMCITABINE; HYDROXYUREA; MUTANT PROTEIN; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTOR E2F; TRANSCRIPTION FACTOR E2F1; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; CELL CYCLE S PHASE; CELL TRANSFORMATION; CONTROLLED STUDY; DRUG SENSITIZATION; EMBRYO; ENZYME ACTIVITY; ENZYME INHIBITION; GENETIC TRANSCRIPTION; HOMOZYGOSITY; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAT; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BONE NEOPLASMS; CARCINOMA, NON-SMALL-CELL LUNG; CELL CYCLE; CELL CYCLE PROTEINS; CELL LINE, TRANSFORMED; CELL LINE, TUMOR; DNA, NEOPLASM; DNA-BINDING PROTEINS; DRUG SYNERGISM; E2F TRANSCRIPTION FACTORS; E2F1 TRANSCRIPTION FACTOR; ENZYME INHIBITORS; FLAVONOIDS; HUMANS; LUNG NEOPLASMS; OSTEOSARCOMA; PHOSPHORYLATION; PIPERIDINES; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; S PHASE; TRANSCRIPTION FACTOR DP1; TRANSCRIPTION FACTORS;

EID: 0242694891     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (72)

1. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell, 81: 323-330, 1995.
2. 1 cyclins. Cell, 73: 1059-1065, 1993.
3. 1-phase progression. Genes Dev., 13: 1501-1512, 1999.
4. Hall, M., and Peters, G. Genetic alterations of cyclins, cyclin-dependent kinases, and cdk inhibitors in human cancer. Adv. Cancer Res., 68: 67-108, 1996.
5. Sherr, C. J. Cancer cell cycles. Science 274: 1672-1677, 1996.
6. Shapiro, G. I., and Harper, J. W. Anticancer drug targets: cell cycle and checkpoint control. J. Clin. Investig., 104: 1645-1653, 1999.
7. Harbour, J. W., and Dean, D. C. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev., 14: 2393-2409, 2000.
8. Dyson, N. The regulation of E2F by pRB-family proteins. Genes Dev., 12: 2245-2262, 1998.
9. Krek, W., Ewen, M. E., Shirodkar, S., Arany, Z., Kaelin, W. G., Jr., and Livingston, D. M. Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase. Cell. 78: 161-172, 1994.
10. Dynlacht, B. D., Flores, O., Lees, J. A., and Harlow, E. Differential regulation of E2F transactivation by cyclin-cdk2 complexes. Genes Dev., 8: 1772-1786, 1994.
11. Xu, M., Sheppard, K. A., Peng, C. Y., Yee, A. S., and Piwinica-Worms, H. Cyclin A/Cdk2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. Mol. Cell. Biol., 14: 8420-8431, 1994.
12. Kitagawa, M., Higashi, H., Suzuki-Takahashi, I., Segawa, K., Hanks, S. K., Taya, Y., Nishimura, S., and Okuyama, A. Phosphorylation of E2F-1 by cyclin A-cdk2. Oncogene, 10: 229-236, 1995.
13. Peeper, D. S., Keblusek, P., Helin, K., Toebes, M., van der Eb, A. J., and Zantema, A. Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro. Oncogene, 10: 39-48, 1995.
14. Krek, W., Xu, G., and Livingston, D. M. Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint. Cell, 83: 1149-1158, 1995.
15. Phillips, A. C., and Vousden, K. H. E2F-1 induced apoptosis. Apoptosis, 6: 173-182, 2001.
16. Chen, Y. N. P., Sharma, S. K., Ramsey, T. M., Jiang, L., Martin, M. S., Baker, K., Adams, P. D., Bair, K. W., and Kaelin, W. G. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc. Natl. Acad. Sci. USA, 96: 4325-4329, 1999.
17. Senderowicz, A. M., and Sausville, E. A. Preclinical and clinical development of cyclin-dependent kinase modulators. J. Natl. Cancer Inst. (Bethesda), 92: 376-387, 2000.
18. Sedlacek, H. H., Czech, J., Naik, R., Kaur, G., Worland, P., Losiewicz, M., Parker, B., Carlson, B., Smith, A., Senderowicz, A., and Sausville, E. A. Flavopiridol (L86 8275; NSC 649890), a new kinase inhibitor for tumor therapy. Int. J. Oncol., 9: 1143-1168, 1996.
19. Kelland, L. R. Flavopiridol, the first cyclin-dependent kinase inhibitor to enter the clinic: current status. Exp. Opin. Investig. Drugs, 9: 2903-2911, 2000.
20. Sedlacek, H. H. Mechanisms of action of flavopiridol. Crit. Rev. Oncol. Hematol., 38: 139-170, 2001.
21. Matranga, C. B., and Shapiro, G. I. Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S phase. Cancer Res., 62: 1707-1717, 2002.
22. Pear, W. S., Nolan, G. P., Scott, M. L., and Baltimore, D. Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. USA, 90: 8392-8396, 1993.
23. Pruschy, M., Wirbelauer, C., Glanzmann, C., Bodis, S., and Krek, W. E2F-1 has properties of a radiosensitizer and its regulation by cyclin A kinase is required for cell survival of fibrosarcoma cells lacking p53. Cell Growth Differ., 10: 141-146, 1999.
24. Verona, R., Moberg, K., Estes, S., Starz, M., Vemon, J. P., and Lees, J. A. E2F activity is regulated by cell cycle-dependent changes in subcellular localization. Mol. Cell. Biol., 17: 7268-7282, 1997.
25. Qin, X. Q., Livingston, D. M., Kaelin, W. G., and Adams, P. D. Deregulated transcription factor E2F-1 expression leads to S phase entry and p53-mediated apoptosis. Proc. Natl. Acad. Sci. USA, 91: 10918-10922, 1994.
26. Field, S. J., Tsai, F. Y., Kuo, F., Zubiaga, A. M., Kaelin, J., W. G., Livingston, D. M., Orkin, S. H., and Greenberg, M. E. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell, 85: 549-561, 1996.
27. Todaro, G. J., and Green, H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J. Cell Biol., 17: 299-313, 1963.
28. Shapiro, G. I., Koestner, D. A., Matranga, C. B., and Rollins, B. J. Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines. Clin. Cancer Res., 5: 2925-2938, 1999.
29. Benotmane, A. M., Hoylaerts, M. F., Collen, D., and Belayew, A. Nonisotopic quantitative analysis of protein-DNA interactions at equilibrium. Anal. Biochem., 250: 181-185, 1997.
30. Janicke, R. U., Walker, P. A., Lin, X. Y., and Porter, A. G. Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis. EMBO J., 15: 6969-6978, 1996.
31. Knudsen, E. S., and Wang, J. Y. Differential regulation of retinoblastoma protein function by specific cdk phosphorylation sites. J. Biol. Chem., 271: 8313-8320, 1996.
32. Kitagawa, M., Higashi, H., Jung, H. K., Suzuki-Takahashi, I., Ikeda, M., Tamai, K., Kato, J. Y., Segawa, K., Yoshida, E., Nishimura, S., and Taya, Y. The consensus motif for phosphorylation by cyclin D1-cdk-4 is different from that for phosphorylation by cyclin A/E-cdk2. EMBO J., 15: 7060-7069, 1996.
33. 1/S cyclin-dependent kinases. J. Biol. Chem., 272: 12738-12746, 1997.
34. Connell-Crowley, L., Harper, J. W., and Goodrich, D. W. Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation, Mol. Biol. Cell, 8: 287-301, 1997.
35. Hirai, H., Roussel, M. F., Kato, J. Y., Ashmun, R. A., and Sherr, C. J. Novel INK4 proteins, p19 and p18, are specific inhibitors of cyclin D-dependent kinases CDK4 and CDK6. Mol. Cell. Biol., 15: 2672-2681, 1995.
36. Grimison, B., Langan, T. A., and Sclafani, R. A. p16INK4A tumor suppressor function in lung cancer cells involves cyclin-dependent kinase 2 inhibition by Cip/Kip protein redistribution. Cell Growth Differ., 11: 507-515, 2000.
37. Sheaff, R. J., Groudine, M., Gordon, M., Roberts, J. M., and Clurman, B. E. Cyclin E-cdk2 is a regulator of p27. Genes Dev., 11: 1464-1478, 1997.
38. Vlach, J., Hennecke, S., and Amati, B. Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J., 16: 5334-5344, 1997.
39. Chao, S. H., and Price, D. H. Flavopiridol inactivates p-TEFb and blocks most RNA polymerase II transcription in vivo. J. Biol. Chem., 276: 31793-31799, 2001.
40. Lam, L. T., Pickeral, O. K., Peng, A. C., Rosenwald, A., Hurt, E. M., Gilmane, J. M., Averett, L. M., Zhao, H., Davis, R. E., Sathyamoorthy, M., Wahl, L. M., Harris, E. D., Mikovits, J. A., Monks, A. P., Hollingshead, M. G., Sausville, E. A., and Staudt, L. M. Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol., 2: research0041. Epub, 2001.
41. Kip1. Nature (Lond.), 404: 782-787, 2000.
42. Cartee, L., Wang, Z., Decker, R. H., Chellappan, S. P., Fusaro, G., Hirsch, K. G., Sankala, H. M., Dent, P., and Grant, S. The cyclin dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12-myristate 13-acetate-induced differentiation and CDKI expression while enhancing apoptosis in human myeloid leukemia cells. Cancer Res., 61: 2583-259, 2001.
43. Motwani, M., Jung, C., Siromak, F. M., She, Y., Shah, M. A., Gonen, M., and Schwartz, G. K. Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in HCTI 16 colon cancer monolayers and xenografts. Clin. Cancer Res., 7: 4209-4219, 2001.
44. cip1/waf1 by caspases is an early event during DNA damage-induced apoptosis. J. Biol. Chem., 273: 19207-19212, 1998.
45. Kip1 mediates apoptosis in endothelial cells through activation of cdk2: role of a caspase cascade. Mol. Cell., 1: 553-563, 1998.
46. waf1/cip1 converts cancer cells from growth arrest to undergoing apoptosis. Oncogene, 18: 1131-1138, 1999.
47. Ma, Y., Cress, D., and Haura, E. B. Flavopiridol-induced apoptosis is mediated through up-regulation of E2F-1 and repression of Mcl-1. Mol. Cancer Ther., 2: 73-81, 2003.
48. Brüsselbach, S., Nettelbeck, D. M., Sedlacek, H. H., and Muller, R. Cell cycle-independent induction of apoptosis by the anti-tumor drug flavopiridol in endothelial cells. Int. J. Cancer, 77: 146-152, 1998.
49. Wu, X., and Levine, A. J. p53 and E2F-1 cooperate to mediate apoptosis. Proc. Natl. Acad. Sci. USA, 91: 3602-3606, 1994.
50. Shan, B., and Lee, W. H. Deregulated expression of E2F-1 induces S phase entry and leads to apoptosis. Mol. Cell. Biol., 14: 8166-8173, 1994.
51. Phillips, A. C., Bates, S., Ryan, K. M., Helin, K., and Vousden, K. H. Induction of DNA synthesis and apoptosis are separable functions of E2F-1. Genes Dev., 11: 846-1666, 1997.
52. Hseih, J. K., Frdersdorf, S., Kouzarides, T., Martin, K., and Lu, X. E2F-I-induced apoptosis requires DNA binding but not transactivation and is inhibited by the retinoblastoma protein through direct interaction. Genes Dev., 11: 1840-1852, 1997.
53. Hunt, K. K., Deng, J., Liu, T. J., Wilson-Heiner, M., Swisher, S. G., Clayman, G., and Hung, M. C. Adenovirus-mediated overexpression of the transcription factor E2F-1 induces apoptosis in human breast and ovarian carcinoma cell lines and does not require p53. Cancer Res., 57: 4722-4726, 1997.
54. Holmberg, C., Helin, K., Sehested, M., and Karlstrom, O. E2F-1-induced p53-independent apoptosis in transgenic mice. Oncogene, 17: 143-155, 1998.
55. Bates, S., Phillips, A. C., Clark, P. A., Stott, F., Peters, G., Ludwig, R. L., and Vousden, K. H. p14 ARF links the tumour suppressors RB and p53. Nature (Lond.), 395: 124-125, 1998.
56. Sherr, C. Tumor surveillance via the ARF-p53 pathway. Genes Dev., 12: 2984-2991, 1998.
57. Mitsudomi, T., Steinberg, S. M., Nau, M. M., Carbone, D., D'Amico, D., Bodner, S., Oie, H. K., Linnoila, R. I., Mulshine, J. L., Minna, J. D., and Gazdar, A. F. p53 gene mutations in non-small cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene, 7: 171-180, 1992.
58. Lissy, N. A., Davis, P. K., Irwin, M., Kaelin, W. G., and Dowdy, S. F. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation. Nature (Lond.), 407: 642-645, 2000.
59. Irwin, M., Marin, M. C., Phillips, A. C., Seelan, R. S., Smith, D. I., Liu, W., Flores, E. R., Tsai, K. Y., Jacks, T., Vousden, K., and Kaelin, W. G. Role for the p53 homologue p73 in E2F-1 induced apoptosis. Nature (Lond.), 407: 645-648, 2000.
60. Stiew, T., and Putzer, B. M., Role of the p53-homologue p73 in E2F-I-induced apoptosis. Nat. Genet., 26: 464-469, 2000.
61. Moroni, M. C., Hickman, E. S., Denchi, E. L., Caprara, G., Colli, E., Cecconi, F., Muller, H., and Helin, K. Apaf-1 is a transcriptional target for E2F and p53. Nat. Cell Biol., 3: 552-558, 2001.
62. Muller, H., Bracken, A. P., Vemell, R., Moroni, M. C., Christians, F., Grassilli, E., Prosperini, E., Vigo, E., Oliner, J. D., and Helin, K. E2Fs regulate the expression of genes involved in differentiation, development, proliferation and apoptosis. Genes Dev., 15: 267-285, 2001.
63. Phillips, A., Emst, M., Bates, S., Rice, N., and Vousden, K. E2F-1 potentiates cell death by blocking antiapoptotic signaling pathways. Mol. Cell, 4: 771-781, 1999.
64. Tanaka, H., Matsumura, I., Ezoe, S., Satoh, Y., Sakamaki, T., Albanese, C., Machii, T., Pestell, R. G., and Kanakura, Y. E2F1 and c-Myc potentiate apoptosis through inhibition of NF-κB activity that facilitates MnSOD-mediated ROS elimination. Mol. Cell, 9: 1017-1029, 2002.
65. Kim, D. M., Koo, S. Y., Jeon, K., Kim, M. H., Lee, J., Hong, C. Y., and Jeong, S. Rapid induction of apoptosis by combination of flavopiridol and tumor necrosis factor (TNF)- or TNF-related apoptosis-inducing ligand in human cancer cell lines. Cancer Res., 63: 549-736, 2003.
66. Jung, C. P., Motwani, M. V., and Schwartz, G. K. Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of the ribonucleotide reductase M2 subunit. Clin. Cancer Res., 7: 2527-2536, 2001.
67. Vandel, L., and Kouzarides, T. Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase, EMBO J., 18: 4280-4291, 1999.
68. Tetsu, O., and McCormick, F. Proliferation of cancer cells despite cdk2 inhibition. Cancer Cell, 3: 233-245, 2003.
69. Katayose, Y., Kim, M., Rakkar, A. N. S., Li, Z., Cowan, K. H., and Seth, P. Promoting apoptosis: a novel activity associated with the cyclin-dependent kinase inhibitor p27. Cancer Res., 57: 5441-5445, 1997.
70. Kip1 overexpression causes apoptotic death of mammalian cells. Oncogene, 1997.
71. 2 roles for cdk2 revealed by inducible expression of a dominant-negative mutant in human cells. Mol. Cell. Biol., 21: 2755-2766, 2001.
72. Shapiro, G. I. Small molecule inhibitors of cyclin-dependent kinases. In: M. Blagosklonny (ed.). Cell Cycle Checkpoints and Cancer. pp. 208-234. Georgetown, TX: Landes Bioscience, 2001.