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Mechanisms of apoptosis induction by nucleoside analogs

Oncogene volume 22, pages 9063–9074 (2003)Cite this article

Abstract

Nucleoside analogs are structurally, metabolically, and pharmacodynamically related agents that nevertheless have diverse biological actions and therapeutic consequences. This class of agents affects the structural integrity of DNA, generally after incorporation during replication or DNA excision repair synthesis, leading to stalled replication forks and chain termination. The DNA damage sensors ATM, ATR and DNA-PK recognize these events. These and other protein kinases activate checkpoint pathways that arrest cell cycle progression, and also signal for DNA repair. In addition, if these survival mechanisms are overwhelmed by the damage caused, a third function of these sensors is to activate signaling pathways that initiate apoptotic processes. A review of the spectrum of responses that are activated by clinically relevant nucleoside analogs begins to provide a mechanistic basis for diverse outcomes in cell viability. Such information, when coupled with an understanding of the intrinsic apoptotic potential of a tumor cell type may provide a rational basis for the design of therapeutic strategies.

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Abbreviations

ara-C:

arabinosylcytosine

dNTP:

deoxynucleotide triphosphate

DNA-PK:

DNA-activated protein kinase

HU:

hydroxyurea

JNK:

c-jun-N-terminal kinase

References

  • Achanta G, Pelicano H, Feng L, Plunkett W and Huang P . (2001). Cancer Res., 61, 8723–8729.

  • Agarwal RP . (1982). Pharmacol. Ther., 17, 399–429.

  • Akinaga S, Sugiyama K and Akiyama T . (2000). Anticancer Drug Des., 15, 43–52.

  • Azuma A, Huang P, Matsuda A and Plunkett W . (2001). Mol. Pharmacol., 59, 725–731.

  • Bellosillo B, Villamor N, Lopez-Guillermo A, Marce S, Bosch F, Campo E, Montserrat E and Colomer D . (2002). Blood, 100, 1810–1816.

  • Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J and Sancar A . (2003). Proc. Natl. Acad. Sci. USA, 100, 1633–1638.

  • Bianchi V, Pontis E and Reichard P . (1992). Exp. Cell Res., 199, 120–128.

  • Brown EJ and Baltimore D . (2003). Genes Dev., 17, 615–628.

  • Budihardjo I, Oliver H, Lutter M, Luo X and Wang X . (1999). Annu. Rev. Cell Dev. Biol., 15, 269–290.

  • Bullock G, Ray S, Reed JC, Krajewski S, Ibrado AM, Huang Y and Bhalla K . (1996). Leukemia, 10, 1731–1740.

  • Buschmann T, Potapova O, Bar-Shira A, Ivanov VN, Fuchs SY, Henderson S, Fried VA, Minamoto T, Alarcon-Vargas D, Pincus MR, Gaarde WA, Holbrook NJ, Shiloh Y and Ronai Z . (2001). Mol. Cell. Biol., 21, 2743–2754.

  • Capasso H, Palermo C, Wan S, Rao H, John UP, O'Connell MJ and Walworth NC . (2002). J. Cell Sci., 115, 4555–4564.

  • Carson DA, Carrera CJ, Wasson DB and Yamanaka H . (1988). Adv. Enzyme Regul., 27, 395–404.

  • Carson DA and Kaye J . (1978). CIBA Found. Symp., 68, 115–133.

  • Carter BZ, Kornblau SM, Tsao T, Wang RY, Schober WD, Milella M, Sung HG, Reed JC and Andreeff M . (2003). Blood epub ahead of print.

  • Cha RS and Kleckner N . (2002). Science, 297, 602–606.

  • Chan TS . (1978). Cell, 14, 523–530.

  • Chauhan D, Li G, Hideshima T, Podar K, Mitsiades C, Mitsiades N, Munshi N, Kharbanda S and Anderson KC . (2003). J. Biol. Chem., 278, 17593–17596.

  • Chen J, Marechal V and Levine AJ . (1993). Mol. Cell. Biol., 13, 4107–4114.

  • Cheson BD, Keating MJ and Plunkett W . (1997). Nucleoside Analogs in Cancer Therapy. Marcel Dekker, Inc.: New York.

    Google Scholar 

  • Chrencik JE, Burgin AB, Pommier Y, Stewart L and Redinbo MR . (2003). J. Biol. Chem., 278, 12461–12466.

  • Cliby WA, Lewis KA, Lilly KK and Kaufmann SH . (2002). J. Biol. Chem., 277, 1599–1606.

  • Cohen A, Doyle D, Martin Jr DW and Ammann AJ . (1976). N. Engl. J. Med., 295, 1449–1454.

  • Cohen A, Gudas LJ, Ammann AJ, Staal GE and Martin Jr DW . (1978b). J. Clin. Invest., 61, 1405–1409.

  • Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R and Martin Jr DW . (1978a). Proc. Natl. Acad. Sci. USA, 75, 472–476.

  • Cox MM, Goodman MF, Kreuzer KN, Sherratt DJ, Sandler SJ and Marians KJ . (2000). Nature, 404, 37–41.

  • Crews KR, Gandhi V, Srivastava DK, Razzouk BI, Tong X, Behm FG, Plunkett W, Raimondi S, Pui C-H, Rubnitz MV, Stewart CF and Ribeiro RC . (2002). J. Clin. Oncol., 20, 4217–4224.

  • Datta R, Oki E, Endo K, Biedermann V, Ren J and Kufe D . (2000). J. Biol. Chem., 275, 31733–31738.

  • Dearden CE, Matutes E and Catovsky D . (2000). Semin. Oncol., 27 (Suppl. 5), 22–26.

  • Dewson G, Snowden RT, Almond JB, Dyer MJ and Cohen GM . (2003). Oncogene, 22, 2643–2654.

  • Durocher D and Jackson SP . (2001). Curr. Opin. Cell Biol., 13, 225–231.

  • Eastman A, Kohn EA, Brown MK, Rathman J, Livingstone M, Blank DH and Gribble GW . (2002). Mol. Cancer Ther., 1, 1067–1078.

  • Eggert A, Grotzer MA, Zuzak TJ, Wiewrodt BR, Ho R, Ikegaki N and Brodeur GM . (2001). Cancer Res., 61, 1314–1319.

  • Elion GB . (1989). Science, 244, 41–47.

  • Eucker J, Schille C, Schmid P, Jakob C, Schetelig J, Kingreen D, Mergenthaler HG, Huhn D, Possinger K and Sezer O . (2002). Anticancer Drugs, 13, 907–913.

  • Faderl S, Gandhi V, Kantajian H and Plunkett W . (2002). Cancer Chemother. Biol. Response Modif., 20, 36–58.

  • Feng L, Achanta G, Pelicano H, Zhang W, Plunkett W and Huang P . (2000). Int. J. Mol. Med., 5, 597–604.

  • Fu WN, Bertoni F, Kelsey SM, McElwaine SM, Cotter FE, Newland AC and Jia L . (2003). Oncogene, 22, 451–455.

  • Fukazawa T, Fujiwara T, Morimoto Y, Shao J, Nishizaki M, Kadowaki Y, Hizuta A, Owen-Schaub LB, Roth JA and Tanaka N . (1999). Oncogene, 18, 2189–2199.

  • Fulda S, Kufer MU, Meyer E, van Valen F, Dockhorn-Dworniczak B and Debatin KM . (2001). Oncogene, 20, 5865–5877.

  • Furuta T, Takemura H, Liao ZY, Aune GJ, Redon C, Sedelnikova OA, Pilch DR, Rogakou EP, Celeste A, Chen HT, Nussenzweig A, Aladjem MI, Bonner WM and Pommier Y . (2003). J. Biol. Chem., 278, 20303–20312.

  • Fink D, Aebi S and Howell SB . (1998). Clin. Cancer Res., 4, 1–6.

  • Genini D, Adachi S, Chao Q, Rose DW, Carrera CJ, Cottam HB, Carson DA and Leoni LM . (2000b). Blood, 96, 3537–3543.

  • Genini D, Budihardjo I, Plunkett W, Wang X, Carrera CJ, Cottam HB, Carson DA and Leoni LM . (2000a). J. Biol. Chem., 275, 29–34.

  • Giblett ER, Ammann AJ, Sandman R, Wara DW and Diamond LK . (1975). Lancet, 2, 1010.

  • Grotzer MA, Eggert A, Zuzak TJ, Janss AJ, Marwaha S, Wiewrodt BR, Ikegaki N, Brodeur GM and Phillips PC . (2000). Oncogene, 19, 4604–4610.

  • Giblett ER, Anderson JE, Cohen F, Pollara B and Meuwissen HJ . (1972). Lancet, 2, 1067.

  • Goodman GR, Burian C, Koziol JA and Saven A . (2003). J. Clin. Oncol., 21, 891–896.

  • Goodman MF . (2000). Trends Biochem. Sci., 25, 189–195.

  • Grant S . (1988). Adv. Cancer Res., 72, 197–233.

  • Grem JL, Takimoto CH, Multani P, Chu E, Ryan D, Chabner BA, Allegra CJ and Johnston PG . (1999). Cancer Chemother. Biol. Response Modif., 18, 1–38.

  • Gunji H, Kharbanda S and Kufe D . (1991). Cancer Res., 51, 741–743.

  • Haaf T . (1995). Pharmacol Ther., 65, 19–46.

  • Harada K, Toyooka S, Shivapurkar N, Maitra A, Reddy JL, Matta H, Miyajima K, Timmons CF, Tomlinson GE, Mastrangelo D, Hay RJ, Chaudhary PM and Gazdar AF . (2002). Cancer Res., 62, 5897–5901.

  • Heffernan TP, Simpson DA, Frank AR, Heinloth AN, Paules RS, Cordeiro-Stone M and Kaufmann WK . (2002). Mol. Cell. Biol., 22, 8552–8561.

  • Heidelberger C, Danenberg PV and Moran RG . (1983). Adv. Enzymol. Relat. Areas Mol. Biol., 54, 58–119.

  • Heinemann V, Xu Y-Z, Chubb S, Hertel LW, Grindey GB and Plunkett W . (1992). Cancer Res., 52, 533–539.

  • Heinemann V, Xu Y-Z, Chubb S, Sen A, Hertel LW, Grindey GB and Plunkett W . (1990). Mol. Pharmacol., 38, 567–572.

  • Hentosh P, Koob R and Blakley RL . (1990). J. Biol. Chem., 265, 4033–4040.

  • Hirao A, Cheung A, Duncan G, Girard PM, Elia AJ, Wakeham A, Okada H, Sarkissian T, Wong JA, Sakai T, De Stanchina E, Bristow RG, Suda T, Lowe SW, Jeggo PA, Elledge SJ and Mak TW . (2002). Mol. Cell. Biol., 22, 6521–6532.

  • Huang P, Chubb S, Hertel LW, Grindey GB and Plunkett W . (1991). Cancer Res., 51, 6110–56111.

  • Huang P, Chubb S and Plunkett W . (1990). J. Biol. Chem., 265, 16617–16625.

  • Huang P and Plunkett W . (1991). Mol. Pharmacol., 39, 449–455.

  • Huang P and Plunkett W . (1995). Cancer Chemother. Pharmacol., 36, 181–188.

  • Huang P, Sandoval A, van den Neste E, Keating MJ and Plunkett W . (2000). Leukemia, 14, 1405–1413.

  • Ibrado AM, Huang Y, Fang G, Liu L and Bhalla K . (1996). Cancer Res., 56, 4743–4748.

  • Ingraham HA, Tseng BY and Goulian M . (1982). Mol. Pharmacol., 21, 211–216.

  • Johnson SA . (2000). Clin. Pharmacokinetics, 39, 5–26.

  • Johnson SA . (2001). Expert Opin. Pharmacother., 2, 929–943.

  • Jones PA and Baylin SB . (2002). Nat. Rev. Genet., 3, 415–428.

  • Kamiya K, Huang P and Plunkett W . (1996). J. Biol. Chem., 271, 19428–19435.

  • Kastan MB, Lim DS, Kim ST, Xu B and Canman C . (2000). Cold Spring Harb. Symp. Quant. Biol., 65, 521–526.

  • Keating MJ . (1997). Clin. Cancer Res., 3, 2598–2604.

  • Keating MJ . (1999a). Clin. Cancer Res., 3 (Part 2), 2598–2604.

  • Keating MJ . (1999b). Semin. Oncol., 26 (Suppl. 14), 107–114.

  • Keith FJ, Bradbury DA, Zhu YM and Russell NH . (1995). Leukemia, 9, 131–138.

  • Kharbanda S, Pandey P, Jin S, Inoue S, Bharti A, Yuan ZM, Weichselbaum R, Weaver D and Kufe D . (1997). Nature, 386, 732–735.

  • Kharbanda S, Pandey P, Ren R, Mayer B, Zon L and Kufe D . (1995). J. Biol. Chem., 270, 30278–30281.

  • Kharbanda S, Saxena S, Yoshida K, Pandey P, Kaneki M, Wang Q, Cheng K, Chen YN, Campbell A, Sudha T, Yuan ZM, Narula J, Weichselbaum R, Nalin C and Kufe D . (2000). J. Biol. Chem., 275, 322–327.

  • Kim CN, Wang X, Huang Y, Ibrado AM, Liu L, Fang G and Bhalla K . (1997). Cancer Res., 57, 3115–3120.

  • Kim ST, Lim DS, Canman CE and Kastan MB . (1999). J. Biol. Chem., 274, 37538–37543.

  • Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, Wang HG, Zhang X, Bullrich F, Croce CM, Rai K, Hines J and Reed JC . (1998). Blood, 91, 3379–3389.

  • Kluck RM, Bossy-Wetzel E, Green DR and Newmeyer DD . (1997). Science, 275, 1132–1136.

  • Kobayashi T, Ruan S, Jabbur JR, Consoli U, Clodi K, Shiku H, Owen-Schaub LB, Andreeff M, Reed JC and Zhang W . (1998). Cell Death Differ., 5, 584–591.

  • Kohn EA, Ruth ND, Brown MK, Livingstone M and Eastman A . (2002). J. Biol. Chem., 277, 26553–26564.

  • Komander D, Kular GS, Bain J, Elliott M, Alessi DR and Van Aalten DM . (2003). Biochem. J. 375, 255–262.

  • Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, Yamada M, Lieberman HB and Wang HG . (2000). Nat. Cell Biol., 2, 1–6.

  • Konopleva M, Konoplev S, Hu W, Zaritskey AY, Afanasiev BV and Andreeff M . (2002a). Leukemia, 16, 1713–1724.

  • Konopleva M, Tari AM, Estrov Z, Harris D, Xie Z, Zhao S, Lopez-Berestein G and Andreeff M . (2000). Blood, 95, 3929–3938.

  • Konopleva M, Zhao S, Hu W, Jiang S, Snell V, Weidner D, Jackson CE, Zhang X, Champlin R, Estey E, Reed JC and Andreeff M . (2002b). Br. J. Haematol., 118, 521–534.

  • Kufe DW, Weichselbaum R, Egan EM, Dahlberg W and Fram RJ . (1984). Mol. Pharmacol., 25, 322–326.

  • Lakin ND and Jackson SP . (1999). Oncogene, 18, 7644–7655.

  • Lees-Miller SP, Godbout R, Chan DW, Weinfeld M, Day III RS, Barron GM and Allalunis-Turner J . (1995). Science, 267, 1183–1185.

  • Leoni LM, Chao Q, Cottam HB, Genini D, Rosenbach M, Carrera CJ, Budihardjo I, Wang X and Carson DA . (1998). Proc. Natl. Acad. Sci. USA, 95, 9567–9571.

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X . (1997). Cell, 91, 479–489.

  • Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, Luo G, Carattini-Rivera S, DeMayo F, Bradley A, Donehower LA and Elledge SJ . (2000). Genes Dev., 14, 1448–1459.

  • Longley DB, Harkin DP and Johnston PG . (2003). Nat. Rev. Cancer, 3, 330–338.

  • Lopez-Girona A, Tanaka K, Chen XB, Baber BA, McGowan CH and Russell P . (2001). Proc. Natl. Acad. Sci. USA, 98, 11289–11294.

  • Massey A, Xu YZ and Karran P . (2001). Curr. Biol., 11, 1142–1146.

  • Miyashita T and Reed JC . (1993). Blood, 81, 151–157.

  • Miyashita T and Reed JC . (1995). Cell, 80, 293–299.

  • Momand J, Zambetti GP, Olson DC, George D and Levine AJ . (1992). Cell, 69, 1237–1245.

  • Muller M, Strand S, Hug H, Heinemann EM, Walczak H, Hofmann WJ, Stremmel W, Krammer PH and Galle PR . (1997). J. Clin. Invest., 99, 403–413.

  • Muller M, Wilder S, Bannasch D, Israeli D, Lehlbach K, Li-Weber M, Friedman SL, Galle PR, Stremmel W, Oren M and Krammer PH . (1998). J. Exp. Med., 188, 2033–2045.

  • O'Brien SM, Kantarjian HM, Cortes J, Beran M, Koller CA, Giles FJ, Lerner S and Keating M . (2001). J. Clin. Oncol., 19, 1414–1420.

  • Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T and Tanaka N . (2000). Science, 288, 1053–1058.

  • Ohno Y, Spriggs D, Matsukage A, Ohno T and Kufe D . (1988). Cancer Res., 48, 1494–1498.

  • Owen-Schaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T, Roth JA, Deisseroth AB, Zhang WW and Kruzel E (1995). Mol. Cell Biol., 15, 3032–3040.

  • Parker WB, Bapat AR, Shen JX, Townsend AJ and Cheng YC . (1988). Mol. Pharmacol., 34, 485–491.

  • Parker WB and Cheng YC . (1990). Pharmacol. Ther., 48, 381–385.

  • Petak I and Houghton J.A. . (2001). Pathol. Oncol. Res., 7, 95–106.

  • Petak I, Danam RP, Tillman DM, Vernes R, Howell SR, Berczi L, Kopper L, Brent TP and Houghton JA . (2003). Cell Death Differ., 10, 211–217.

  • Petak I, Tillman DM and Houghton JA . (2000). Clin. Cancer Res., 6, 4432–4441.

  • Pinedo HM and Peters GF . (1988). J. Clin. Oncol., 10, 1653–1664.

  • Plunkett W, Benjamin RS, Keating MJ and Freireich EJ . (1982). Cancer Res., 42, 2092–2096.

  • Plunkett W and Gandhi V . (2001). Cancer Chemother. Biol. Response Modif., 19, 21–45.

  • Plunkett W, Huang P, Searcy CE and Gandhi V . (1996). Semin. Oncol., 23 (Suppl. 10), 3–15.

  • Pourquier P, Takebayashi Y, Urasaki Y, Gioffre C, Kohlhagen G and Pommier Y . (2000). Proc. Natl. Acad. Sci. USA, 97, 1885–1890.

  • Raina D, Mishra N, Kumar S, Kharbanda S, Saxena S and Kufe D . (2002). Mol. Pharmacol., 61, 1489–1495.

  • Rao VA and Plunkett W . (2002). Proc. Am. Assoc. Cancer Res., 43, 797.

  • Rao VA and Plunkett W . (2003). Clin. Cancer Res., 9, 3204–3212.

  • Rodriguez Jr CO, Stellrecht CM and Gandhi V . (2003). Blood, 102, 1842–1848.

  • Roos-Mattjus P, Hopkins KM, Oestreich AJ, Vroman BT, Johnson KL, Naylor S, Lieberman HB and Karnitz LM . (2003). J. Biol. Chem., 278, 24428–24437.

  • Roos-Mattjus P, Vroman BT, Burtelow MA, Rauen M, Eapen AK and Karnitz LM . (2002). J. Biol. Chem., 277, 43809–43812.

  • Sampath D and Plunkett W . (2000). Cancer Res., 60, 6408–6415.

  • Sampath D, Shi Z and Plunkett W . (2002). Mol. Pharmacol., 62, 680–688.

  • Sandoval A, Consoli U and Plunkett W . (1996). Clin. Cancer Res., 2, 1731–1741.

  • Santini V, Kantarjian HM and Issa JP . (2001). Ann. Intern. Med., 134, 573–586.

  • Santoro A, Bredenfeld H, Devizzi L, Tesch, Bonfante V, Viviani S, Fiedler F, Soto Parra H, Benoehr C, Pacini M, Bonadonna G and Diehl V . (2000). J. Clin. Oncol., 18, 2615–2619.

  • Sato S, Fujita N and Tsuruo T . (2002). Oncogene, 21, 1727–1738.

  • Seto S, Carrera CJ, Kubota M, Wasson DM and Carson DA . (1985). J. Clin. Invest., 75, 377–383.

  • Saven A, Burian C, Koziol JA and Piro LD . (1998). Blood, 92, 1918–1926.

  • Schweitzer BI, Mikita T, Kellogg GW, Gardner KH and Beardsley GP . (1994). Biochemistry, 33, 11460–11475.

  • Seto S, Carrera CJ, Kubota M, Wasson DM and Carson DA . (1985). J. Clin. Invest., 75, 377–383.

  • Seto S, Carrera CJ, Wasson DB and Carson DA . (1986). J. Immunol., 136, 2839–2843.

  • Shafman T, Khanna KK, Kedar P, Spring K, Kozlov S, Yen T, Hobson K, Gatei M, Zhang N, Watters D, Egerton M, Shiloh Y, Kharbanda S, Kufe D and Lavin MF . (1997). Nature, 387, 520–523.

  • Shao RG, Cao CX, Shimizu T, O'Connor PM, Kohn KW and Pommier Y . (1997). Cancer Res., 57, 4029–4035.

  • Shi Z, Azuma A, Sampath D, Li YX, Huang P and Plunkett W . (2001). Cancer Res., 61, 1065–1072.

  • Shiloh Y . (2001). Curr. Opin. Genet Dev., 11, 71–77.

  • Snyder RD, van Houten B and Regan JD . (1984). Chem. Biol. Interact., 50, 1–14.

  • Sogo JM, Lopes M and Foiani M . (2002). Science, 297, 599–602.

  • Storniolo AM, Enas NH, Brown CA, Voi M, Rothenberg ML and Schilsky R . (1999). Cancer, 85, 1261–1268.

  • Sugiyama K, Shimizu M, Akiyama T, Tamaoki T, Yamaguchi K, Takahashi R, Eastman A, and Akinaga S . (2000). Int. J. Cancer, 85, 703–709.

  • Sugimoto K, Tamayose K, Takagi M, Yamada K, Sasaki M, Mizutani S and Oshimi K . (2000). Br. J. Haematol., 110, 819–825.

  • Tempero M, Plunkett W, Van Haperen VR, Hainsworth J, Hochster H, Lenzi R and Abbruzzese J . (2003). J. Clin. Oncol. 21, 3402–3408.

  • Tibbetts RS, Brumbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY, Taya Y, Prives C and Abraham RT . (1999). Genes Dev., 13, 152–157.

  • Townsend A and Cheng Y-C . (1987). Mol. Pharmacol., 32, 330–339.

  • Tseng WC, Derse D, Cheng YC, Brockman RW and Bennett Jr LL . (1982). Mol. Pharmacol., 21, 474–477.

  • Ueki T, Takeuchi T, Nishimatsu H, Kajiwara T, Moriyama N, Narita Y, Kawabe K, Ueki K and Kitamura T . (2001). Int. J. Cancer, 91, 673–679.

  • Wang JL, Wang X, Wang H, Iliakis G and Wang Y . (2002). Cell Cycle, 1, 267–272.

  • Ward IM and Chen J . (2001). J. Biol. Chem., 276, 47759–47762.

  • Wen J, Ramadevi N, Nguyen D, Perkins C, Worthington E and Bhalla K . (2000). Blood, 96, 3900–3906.

  • Yamauchi T, Nowak BJ, Keating MJ and Plunkett W . (2001). Clin. Cancer Res., 7, 3580–3589.

  • Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP and Wang X . (1997). Science, 275, 1129–1132.

  • Yang S-W, Huang P, Plunkett W, Becker FF and Chan JYH . (1992). J. Biol. Chem., 267, 2345–2349.

  • Yin MB, Hapke G, Wu J, Azrak RG, Frank C, Wrzosek C and Rustum YM . (2002). Biochem. Biophys. Res. Commun., 295, 435–444.

  • Yin XM . (2000). Cell Res., 10, 161–167.

  • Yoshida K, Komatsu K, Wang HG and Kufe D . (2002). Mol. Cell. Biol. 22, 3292–3300.

  • Yoshida K, Weichselbaum R, Kharbanda S and Kufe D . (2000). Mol. Cell. Biol., 20, 5370–5380.

  • Yu J, Wang Z, Kinzler KW, Vogelstein B and Zhang L . (2003). Proc. Natl. Acad. Sci. USA, 100, 1931–1936.

  • Yuan ZM, Huang Y, Ishiko T, Kharbanda S, Weichselbaum R and Kufe D . (1997). Proc. Natl. Acad. Sci. USA, 94, 1437–1440.

  • Yuan ZM, Kharbanda S and Kufe D . (1995). Biochemistry, 34, 4908.

  • Zachos G, Rainey MD and Gillespie DA . (2003). EMBO J., 22, 713–723.

  • Zhao H and Piwnica-Worms H . (2001). Mol. Cell. Biol., 21, 4129–4139.

  • Zhou BB and Elledge SJ . (2000). Nature, 408, 433–439.

  • Zhu WG, Lakshmanan RR, Beal MD and Otterson GA . (2001). Cancer Res., 61, 1327–1333.

  • Zinzani PL, Baliva G, Magagnoli M, Bendandi M, Modugno G, Gherlinzoni Fraternali F, Orcioni GF, Ascani S, Simoni R, Pileri AS and Tura S . (2000). J. Clin. Oncol., 18, 2603–2606.

  • Zou H, Henzel WJ, Liu X, Lutschg A and Wang X . (1997). Cell, 90, 405–413.

  • Zou L, Cortez D and Elledge SJ . (2002). Genes Dev., 16, 198–208.

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Acknowledgements

Portions of the work described from the authors' laboratories were supported by Grants CA28596, CA32839, CA55164, and CA81534 from the National Cancer Institute, NIH.

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    Deepa Sampath, V Ashutosh Rao & William Plunkett

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Sampath, D., Rao, V. & Plunkett, W. Mechanisms of apoptosis induction by nucleoside analogs. Oncogene 22, 9063–9074 (2003). https://doi.org/10.1038/sj.onc.1207229

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