Bim Upregulation by Histone Deacetylase Inhibitors Mediates Interactions with the Bcl-2 Antagonist ABT-737: Evidence for Distinct Roles for Bcl-2, Bcl-x_L, and Mcl-1

REFERENCES

• Adams, J. M., and S. Cory. 2007. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26:1324–1337.
   PubMed Web of Science ®Google Scholar
• Ambrosini, G., S. L. Seelman, and G. K. Schwartz. 2009. Differentiation-related gene-1 decreases Bim stability by proteasome-mediated degradation. Cancer Res. 69:6115–6121.
   PubMedGoogle Scholar
• Bolden, J. E., M. J. Peart, and R. W. Johnstone. 2006. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5:769–784.
   PubMed Web of Science ®Google Scholar
• Brinkmann, H., A. L. Dahler, C. Popa, M. M. Serewko, P. G. Parsons, B. G. Gabrielli, A. J. Burgess, and N. A. Saunders. 2001. Histone hyperacetylation induced by histone deacetylase inhibitors is not sufficient to cause growth inhibition in human dermal fibroblasts. J. Biol. Chem. 276:22491–22499.
   PubMedGoogle Scholar
• Cartron, P. F., T. Gallenne, G. Bougras, F. Gautier, F. Manero, P. Vusio, K. Meflah, F. M. Vallette, and P. Juin. 2004. The first alpha helix of Bax plays a necessary role in its ligand-induced activation by the BH3-only proteins Bid and PUMA. Mol. Cell 16:807–818.
   PubMed Web of Science ®Google Scholar
• Certo, M., V. G. Moore, M. Nishino, G. Wei, S. Korsmeyer, S. A. Armstrong, and A. Letai. 2006. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9:351–365.
   PubMed Web of Science ®Google Scholar
• Chauhan, D., M. Velankar, M. Brahmandam, T. Hideshima, K. Podar, P. Richardson, R. Schlossman, I. Ghobrial, N. Raje, N. Munshi, and K. C. Anderson. 2007. A novel Bcl-2/Bcl-XL/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma. Oncogene 26:2374–2380.
   PubMed Web of Science ®Google Scholar
• Chen, L., S. N. Willis, A. Wei, B. J. Smith, J. I. Fletcher, M. G. Hinds, P. M. Colman, C. L. Day, J. M. Adams, and D. C. Huang. 2005. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell 17:393–403.
   PubMed Web of Science ®Google Scholar
• Chen, S., Y. Dai, H. Harada, P. Dent, and S. Grant. 2007. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Cancer Res. 67:782–791.
   PubMed Web of Science ®Google Scholar
• Cheng, E. H., M. C. Wei, S. Weiler, R. A. Flavell, T. W. Mak, T. Lindsten, and S. J. Korsmeyer. 2001. BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell 8:705–711.
   PubMed Web of Science ®Google Scholar
• Concannon, C. G., B. F. Koehler, C. Reimertz, B. M. Murphy, C. Bonner, N. Thurow, M. W. Ward, A. Villunger, A. Strasser, D. Kogel, and J. H. Prehn. 2007. Apoptosis induced by proteasome inhibition in cancer cells: predominant role of the p53/PUMA pathway. Oncogene 26:1681–1692.
   PubMed Web of Science ®Google Scholar
• Cory, S., and J. M. Adams. 2002. The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2:647–656.
   PubMed Web of Science ®Google Scholar
• Cory, S., and J. M. Adams. 2005. Killing cancer cells by flipping the Bcl-2/Bax switch. Cancer Cell 8:5–6.
   PubMed Web of Science ®Google Scholar
• Dai, Y., S. Chen, L. B. Kramer, V. L. Funk, P. Dent, and S. Grant. 2008. Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells. Clin. Cancer Res. 14:549–558.
   PubMed Web of Science ®Google Scholar
• Dai, Y., S. Chen, C. A. Venditti, X. Y. Pei, T. K. Nguyen, P. Dent, and S. Grant. 2008. Vorinostat synergistically potentiates MK-0457 lethality in chronic myelogenous leukemia cells sensitive and resistant to imatinib mesylate. Blood 112:793–804.
   PubMed Web of Science ®Google Scholar
• Dai, Y., P. Dent, and S. Grant. 2003. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes mitochondrial dysfunction and apoptosis induced by 7-hydroxystaurosporine and mitogen-activated protein kinase kinase inhibitors in human leukemia cells that ectopically express Bcl-2 and Bcl-xL. Mol. Pharmacol. 64:1402–1409.
   PubMed Web of Science ®Google Scholar
• Dai, Y., M. Rahmani, P. Dent, and S. Grant. 2005. Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF-κB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1 activation. Mol. Cell. Biol. 25:5429–5444.
   PubMed Web of Science ®Google Scholar
• Del Gazo Moore, V., J. R. Brown, M. Certo, T. M. Love, C. D. Novina, and A. Letai. 2007. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J. Clin. Investig. 117:112–121.
   PubMedGoogle Scholar
• Del Gazo Moore, V., K. D. Schlis, S. E. Sallan, S. A. Armstrong, and A. Letai. 2008. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood 111:2300–2309.
   PubMedGoogle Scholar
• Deng, J., N. Carlson, K. Takeyama, P. Dal Cin, M. Shipp, and A. Letai. 2007. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell 12:171–185.
   PubMed Web of Science ®Google Scholar
• Deng, J., T. Shimamura, S. Perera, N. E. Carlson, D. Cai, G. I. Shapiro, K. K. Wong, and A. Letai. 2007. Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion. Cancer Res. 67:11867–11875.
   PubMed Web of Science ®Google Scholar
• Derenne, S., B. Monia, N. M. Dean, J. K. Taylor, M. J. Rapp, J. L. Harousseau, R. Bataille, and M. Amiot. 2002. Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-xL is an essential survival protein of human myeloma cells. Blood 100:194–199.
   PubMed Web of Science ®Google Scholar
• Ewings, K. E., K. Hadfield-Moorhouse, C. M. Wiggins, J. A. Wickenden, K. Balmanno, R. Gilley, K. Degenhardt, E. White, and S. J. Cook. 2007. ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL. EMBO J. 26:2856–2867.
   PubMed Web of Science ®Google Scholar
• Fiskus, W., M. Pranpat, P. Bali, M. Balasis, S. Kumaraswamy, S. Boyapalle, K. Rocha, J. Wu, F. Giles, P. W. Manley, P. Atadja, and K. Bhalla. 2006. Combined effects of novel tyrosine kinase inhibitor AMN107 and histone deacetylase inhibitor LBH589 against Bcr-Abl-expressing human leukemia cells. Blood 108:645–652.
   PubMed Web of Science ®Google Scholar
• Flinterman, M., L. Guelen, S. Ezzati-Nik, R. Killick, G. Melino, K. Tominaga, J. S. Mymryk, J. Gaken, and M. Tavassoli. 2005. E1A activates transcription of p73 and Noxa to induce apoptosis. J. Biol. Chem. 280:5945–5959.
   PubMed Web of Science ®Google Scholar
• Gavathiotis, E., M. Suzuki, M. L. Davis, K. Pitter, G. H. Bird, S. G. Katz, H. C. Tu, H. Kim, E. H. Cheng, N. Tjandra, and L. D. Walensky. 2008. BAX activation is initiated at a novel interaction site. Nature 455:1076–1081.
   PubMed Web of Science ®Google Scholar
• Green, D. R. 2006. At the gates of death. Cancer Cell 9:328–330.
   PubMed Web of Science ®Google Scholar
• Guo, Y., M. C. Schoell, and R. S. Freeman. 2009. The von Hippel-Lindau protein sensitizes renal carcinoma cells to apoptotic stimuli through stabilization of BIMEL. Oncogene 28:1864–1874.
   PubMedGoogle Scholar
• Hann, C. L., V. C. Daniel, E. A. Sugar, I. Dobromilskaya, S. C. Murphy, L. Cope, X. Lin, J. S. Hierman, D. L. Wilburn, D. N. Watkins, and C. M. Rudin. 2008. Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer. Cancer Res. 68:2321–2328.
   PubMed Web of Science ®Google Scholar
• Hsu, Y. T., and R. J. Youle. 1997. Nonionic detergents induce dimerization among members of the Bcl-2 family. J. Biol. Chem. 272:13829–13834.
   PubMed Web of Science ®Google Scholar
• Huang, D. C., and A. Strasser. 2000. BH3-only proteins: essential initiators of apoptotic cell death. Cell 103:839–842.
   PubMed Web of Science ®Google Scholar
• Huang, S., and F. A. Sinicrope. 2008. BH3 mimetic ABT-737 potentiates TRAIL-mediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells. Cancer Res. 68:2944–2951.
   PubMed Web of Science ®Google Scholar
• Inoue, S., J. Riley, T. W. Gant, M. J. Dyer, and G. M. Cohen. 2007. Apoptosis induced by histone deacetylase inhibitors in leukemic cells is mediated by Bim and Noxa. Leukemia 21:1773–1782.
   PubMed Web of Science ®Google Scholar
• Jeffers, J. R., E. Parganas, Y. Lee, C. Yang, J. Wang, J. Brennan, K. H. MacLean, J. Han, T. Chittenden, J. N. Ihle, P. J. McKinnon, J. L. Cleveland, and G. P. Zambetti. 2003. Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell 4:321–328.
   PubMed Web of Science ®Google Scholar
• Kang, M. H., Z. Wan, Y. H. Kang, R. Sposto, and C. P. Reynolds. 2008. Mechanism of synergy of N-(4-hydroxyphenyl)retinamide and ABT-737 in acute lymphoblastic leukemia cell lines: Mcl-1 inactivation. J. Natl. Cancer Inst. 100:580–595.
   PubMedGoogle Scholar
• Kim, H., M. Rafiuddin-Shah, H. C. Tu, J. R. Jeffers, G. P. Zambetti, J. J. Hsieh, and E. H. Cheng. 2006. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat. Cell Biol. 8:1348–1358.
   PubMed Web of Science ®Google Scholar
• Konopleva, M., R. Contractor, T. Tsao, I. Samudio, P. P. Ruvolo, S. Kitada, X. Deng, D. Zhai, Y. X. Shi, T. Sneed, M. Verhaegen, M. Soengas, V. R. Ruvolo, T. McQueen, W. D. Schober, J. C. Watt, T. Jiffar, X. Ling, F. C. Marini, D. Harris, M. Dietrich, Z. Estrov, J. McCubrey, W. S. May, J. C. Reed, and M. Andreeff. 2006. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 10:375–388.
   PubMed Web of Science ®Google Scholar
• Kuroda, J., S. Kimura, A. Strasser, M. Andreeff, L. A. O'Reilly, E. Ashihara, Y. Kamitsuji, A. Yokota, E. Kawata, M. Takeuchi, R. Tanaka, Y. Tabe, M. Taniwaki, and T. Maekawa. 2007. Apoptosis-based dual molecular targeting by INNO-406, a second-generation Bcr-Abl inhibitor, and ABT-737, an inhibitor of antiapoptotic Bcl-2 proteins, against Bcr-Abl-positive leukemia. Cell Death. Differ. 14:1667–1677.
   PubMed Web of Science ®Google Scholar
• Kuroda, J., H. Puthalakath, M. S. Cragg, P. N. Kelly, P. Bouillet, D. C. Huang, S. Kimura, O. G. Ottmann, B. J. Druker, A. Villunger, A. W. Roberts, and A. Strasser. 2006. Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc. Natl. Acad. Sci. USA 103:14907–14912.
   PubMed Web of Science ®Google Scholar
• Kuwana, T., L. Bouchier-Hayes, J. E. Chipuk, C. Bonzon, B. A. Sullivan, D. R. Green, and D. D. Newmeyer. 2005. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol. Cell 17:525–535.
   PubMed Web of Science ®Google Scholar
• Lee, E. F., P. E. Czabotar, B. J. Smith, K. Deshayes, K. Zobel, P. M. Colman, and W. D. Fairlie. 2007. Crystal structure of ABT-737 complexed with Bcl-xL: implications for selectivity of antagonists of the Bcl-2 family. Cell Death Differ. 14:1711–1713.
   PubMed Web of Science ®Google Scholar
• Lee, E. F., P. E. Czabotar, H. Yang, B. E. Sleebs, G. Lessene, P. M. Colman, B. J. Smith, and W. D. Fairlie. 2 September 2009. Conformational changes in BCL-2 pro-survival proteins determine their capacity to bind ligands. J. Biol. Chem. [Epub ahead of print.]
   Google Scholar
• Letai, A. 2005. BCL-2: found bound and drugged! Trends Mol. Med. 11:442–444.
   PubMed Web of Science ®Google Scholar
• Letai, A. 2005. Pharmacological manipulation of Bcl-2 family members to control cell death. J. Clin. Investig. 115:2648–2655.
   PubMed Web of Science ®Google Scholar
• Letai, A., M. C. Bassik, L. D. Walensky, M. D. Sorcinelli, S. Weiler, and S. J. Korsmeyer. 2002. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2:183–192.
   PubMed Web of Science ®Google Scholar
• Letai, A., M. D. Sorcinelli, C. Beard, and S. J. Korsmeyer. 2004. Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell 6:241–249.
   PubMed Web of Science ®Google Scholar
• Letai, A. G. 2008. Diagnosing and exploiting cancer's addiction to blocks in apoptosis. Nat. Rev. Cancer 8:121–132.
   PubMed Web of Science ®Google Scholar
• Li, H., H. Zhu, C. J. Xu, and J. Yuan. 1998. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501.
   PubMed Web of Science ®Google Scholar
• Lin, X., S. Morgan-Lappe, X. Huang, L. Li, D. M. Zakula, L. A. Vernetti, S. W. Fesik, and Y. Shen. 2007. ‘Seed’ analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737. Oncogene 26:3972–3979.
   PubMed Web of Science ®Google Scholar
• Lindemann, R. K., A. Newbold, K. F. Whitecross, L. A. Cluse, A. J. Frew, L. Ellis, S. Williams, A. P. Wiegmans, A. E. Dear, C. L. Scott, M. Pellegrini, A. Wei, V. M. Richon, P. A. Marks, S. W. Lowe, M. J. Smyth, and R. W. Johnstone. 2007. Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma. Proc. Natl. Acad. Sci. USA 104:8071–8076.
   PubMed Web of Science ®Google Scholar
• Mei, Y., W. Du, Y. Yang, and M. Wu. 2005. Puma(*)Mcl-1 interaction is not sufficient to prevent rapid degradation of Mcl-1. Oncogene 24:7224–7237.
   PubMed Web of Science ®Google Scholar
• O'Connor, L., A. Strasser, L. A. O'Reilly, G. Hausmann, J. M. Adams, S. Cory, and D. C. Huang. 1998. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 17:384–395.
   PubMed Web of Science ®Google Scholar
• Oltersdorf, T., S. W. Elmore, A. R. Shoemaker, R. C. Armstrong, D. J. Augeri, B. A. Belli, M. Bruncko, T. L. Deckwerth, J. Dinges, P. J. Hajduk, M. K. Joseph, S. Kitada, S. J. Korsmeyer, A. R. Kunzer, A. Letai, C. Li, M. J. Mitten, D. G. Nettesheim, S. Ng, P. M. Nimmer, J. M. O'Connor, A. Oleksijew, A. M. Petros, J. C. Reed, W. Shen, S. K. Tahir, C. B. Thompson, K. J. Tomaselli, B. Wang, M. D. Wendt, H. Zhang, S. W. Fesik, and S. H. Rosenberg. 2005. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435:677–681.
   PubMed Web of Science ®Google Scholar
• Pei, X. Y., Y. Dai, S. Tenorio, J. Lu, H. Harada, P. Dent, and S. Grant. 2007. MEK1/2 inhibitors potentiate UCN-01 lethality in human multiple myeloma cells through a Bim-dependent mechanism. Blood 110:2092–2101.
   PubMedGoogle Scholar
• Perez-Galan, P., G. Roue, N. Villamor, E. Montserrat, E. Campo, and D. Colomer. 2006. The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Blood 107:257–264.
   PubMed Web of Science ®Google Scholar
• Raje, N., S. Kumar, T. Hideshima, A. Roccaro, K. Ishitsuka, H. Yasui, N. Shiraishi, D. Chauhan, N. C. Munshi, S. R. Green, and K. C. Anderson. 2005. Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma. Blood 106:1042–1047.
   PubMed Web of Science ®Google Scholar
• Reed, J. C. 1997. Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies. Semin. Hematol. 34:9–19.
   PubMed Web of Science ®Google Scholar
• Reed, J. C. 2006. Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death Differ. 13:1378–1386.
   PubMed Web of Science ®Google Scholar
• Reed, J. C., and M. Pellecchia. 2005. Apoptosis-based therapies for hematologic malignancies. Blood 106:408–418.
   PubMed Web of Science ®Google Scholar
• Shelton, S. N., M. E. Shawgo, and J. D. Robertson. 2009. Cleavage of bid by executioner caspases mediates feed forward amplification of mitochondrial outer membrane permeabilization during genotoxic stress-induced apoptosis in Jurkat cells. J. Biol. Chem. 284:11247–11255.
   PubMed Web of Science ®Google Scholar
• Shimazu, T., K. Degenhardt, Nur-E-Kamal, J. Zhang, T. Yoshida, Y. Zhang, R. Mathew, E. White, and M. Inouye. 2007. NBK/BIK antagonizes MCL-1 and BCL-XL and activates BAK-mediated apoptosis in response to protein synthesis inhibition. Genes Dev. 21:929–941.
   PubMedGoogle Scholar
• Tahir, S. K., X. Yang, M. G. Anderson, S. E. Morgan-Lappe, A. V. Sarthy, J. Chen, R. B. Warner, S. C. Ng, S. W. Fesik, S. W. Elmore, S. H. Rosenberg, and C. Tse. 2007. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res. 67:1176–1183.
   PubMed Web of Science ®Google Scholar
• Tajeddine, N., L. Galluzzi, O. Kepp, E. Hangen, E. Morselli, L. Senovilla, N. Araujo, G. Pinna, N. Larochette, N. Zamzami, N. Modjtahedi, A. Harel-Bellan, and G. Kroemer. 2008. Hierarchical involvement of Bak, VDAC1 and Bax in cisplatin-induced cell death. Oncogene 27:4221–4232.
   PubMed Web of Science ®Google Scholar
• Tse, C., A. R. Shoemaker, J. Adickes, M. G. Anderson, J. Chen, S. Jin, E. F. Johnson, K. C. Marsh, M. J. Mitten, P. Nimmer, L. Roberts, S. K. Tahir, Y. Xiao, X. Yang, H. Zhang, S. Fesik, S. H. Rosenberg, and S. W. Elmore. 2008. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68:3421–3428.
   PubMed Web of Science ®Google Scholar
• van Delft, M. F., A. H. Wei, K. D. Mason, C. J. Vandenberg, L. Chen, P. E. Czabotar, S. N. Willis, C. L. Scott, C. L. Day, S. Cory, J. M. Adams, A. W. Roberts, and D. C. Huang. 2006. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 10:389–399.
   PubMed Web of Science ®Google Scholar
• Villunger, A., E. M. Michalak, L. Coultas, F. Mullauer, G. Bock, M. J. Ausserlechner, J. M. Adams, and A. Strasser. 2003. p53- and drug-induced apoptotic responses mediated by BH3-only proteins Puma and Noxa. Science 302:1036–1038.
   PubMed Web of Science ®Google Scholar
• Wei, M. C., W. X. Zong, E. H. Cheng, T. Lindsten, V. Panoutsakopoulou, A. J. Ross, K. A. Roth, G. R. MacGregor, C. B. Thompson, and S. J. Korsmeyer. 2001. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730.
   PubMed Web of Science ®Google Scholar
• Willis, S. N., L. Chen, G. Dewson, A. Wei, E. Naik, J. I. Fletcher, J. M. Adams, and D. C. Huang. 2005. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 19:1294–1305.
   PubMed Web of Science ®Google Scholar
• Willis, S. N., J. I. Fletcher, T. Kaufmann, M. F. van Delft, L. Chen, P. E. Czabotar, H. Ierino, E. F. Lee, W. D. Fairlie, P. Bouillet, A. Strasser, R. M. Kluck, J. M. Adams, and D. C. Huang. 2007. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315:856–859.
   PubMed Web of Science ®Google Scholar
• Zhai, D., C. Jin, Z. Huang, A. C. Satterthwait, and J. C. Reed. 2008. Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family proteins Bcl-B and Mcl-1. J. Biol. Chem. 283:9580–9586.
   PubMed Web of Science ®Google Scholar
• Zhai, D., C. Jin, A. C. Satterthwait, and J. C. Reed. 2006. Comparison of chemical inhibitors of antiapoptotic Bcl-2-family proteins. Cell Death Differ. 13:1419–1421.
   PubMed Web of Science ®Google Scholar
• Zhang, W., M. Konopleva, V. R. Ruvolo, T. McQueen, R. L. Evans, W. G. Bornmann, J. McCubrey, J. Cortes, and M. Andreeff. 2008. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia 22:808–818.
   PubMed Web of Science ®Google Scholar
• Zhao, Y., J. Tan, L. Zhuang, X. Jiang, E. T. Liu, and Q. Yu. 2005. Inhibitors of histone deacetylases target the Rb-E2F1 pathway for apoptosis induction through activation of proapoptotic protein Bim. Proc. Natl. Acad. Sci. USA 102:16090–16095.
   PubMed Web of Science ®Google Scholar
• Zong, W. X., T. Lindsten, A. J. Ross, G. R. MacGregor, and C. B. Thompson. 2001. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 15:1481–1486.
   PubMed Web of Science ®Google Scholar