Advanced search
Publication Cover
Expert Opinion on Therapeutic Targets Volume 12, 2008 - Issue 8
Submit an article Journal homepage
57
Views
3
CrossRef citations to date
0
Altmetric
Review

IAPs as therapeutic targets in haematological malignancies

SMC Langemeijer Radboud University Medical Centre, Nijmegen Centre for Molecular Life Sciences (NCMLS), Central Haematology Laboratory, Department CHL-462, Geert Grooteplein zuid 8, 6525 GA Nijmegen, The Netherlands +31 24 3610372; +31 24 3610373; [email protected]
, MD,
AO de Graaf Radboud University Medical Centre, Nijmegen Centre for Molecular Life Sciences (NCMLS), Central Haematology Laboratory, Department CHL-462, Geert Grooteplein zuid 8, 6525 GA Nijmegen, The Netherlands +31 24 3610372; +31 24 3610373; [email protected]
, PhD &
JH Jansen Radboud University Medical Centre, Nijmegen Centre for Molecular Life Sciences (NCMLS), Central Haematology Laboratory, Department CHL-462, Geert Grooteplein zuid 8, 6525 GA Nijmegen, The Netherlands +31 24 3610372; +31 24 3610373; [email protected]
, PhD
Pages 981-993 | Published online: 12 Jul 2008

Bibliography

  • Lacasse EC, Baird S, Korneluk RG, MacKenzie AE. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 1998;17:3247-59
  • Salvesen GS, Duckett CS. IAP proteins: blocking the road to death's door. Nat Rev Mol Cell Biol 2002;3:401-10
  • Sun C, Cai M, Gunasekera AH, et al. NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Nature 1999;401:818-22
  • Huang H, Joazeiro CA, Bonfoco E, et al. The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7. J Biol Chem 2000;275:26661-4
  • Shin H, Okada K, Wilkinson JC, et al. Identification of ubiquitination sites on the X-linked inhibitor of apoptosis protein. Biochem J 2003;373:965-71
  • Conze DB, Albert L, Ferrick DA, et al. Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo. Mol Cell Biol 2005;25:3348-56
  • Suzuki Y, Nakabayashi Y, Takahashi R. Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proc Natl Acad Sci USA 2001;98:8662-7
  • Yang Y, Fang S, Jensen JP, et al. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 2000;288:874-7
  • Jesenberger V, Jentsch S. Deadly encounter: ubiquitin meets apoptosis. Nat Rev Mol Cell Biol 2002;3:112-21
  • Li X, Yang Y, Ashwell JD. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 2002;416:345-7
  • Holcik M, Gibson H, Korneluk RG. XIAP: apoptotic brake and promising therapeutic target. Apoptosis 2001;6:253-61
  • Deveraux QL, Takahashi R, Salvesen GS, Reed JC. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 1997;388:300-4
  • Tenev T, Zachariou A, Wilson R, et al. IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. Nat Cell Biol 2005;7:70-7
  • Eckelman BP, Salvesen GS, Scott FL. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep 2006;7:988-94
  • Deveraux QL, Roy N, Stennicke HR, et al. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 1998;17:2215-23
  • Deveraux QL, Leo E, Stennicke HR, et al. Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J 1999;18:5242-51
  • Scott FL, Denault JB, Riedl SJ, et al. XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 2005;24:645-55
  • Huang Y, Park YC, Rich RL, et al. Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell 2001;104:781-90
  • Suzuki Y, Nakabayashi Y, Nakata K, et al. X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes. J Biol Chem 2001;276:27058-63
  • Takahashi R, Deveraux Q, Tamm I, et al. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem 1998;273:7787-90
  • Riedl SJ, Renatus M, Schwarzenbacher R, et al. Structural basis for the inhibition of caspase-3 by XIAP. Cell 2001;104:791-800
  • Bratton SB, Lewis J, Butterworth M, et al. XIAP inhibition of caspase-3 preserves its association with the Apaf-1 apoptosome and prevents. Cell Death Differ 2002;9:881-92
  • Zou H, Yang R, Hao J, et al. Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP. J Biol Chem 2003;278:8091-8
  • Sun C, Cai M, Meadows RP, et al. NMR structure and mutagenesis of the third Bir domain of the inhibitor of apoptosis protein XIAP. J Biol Chem 2000;275:33777-81
  • Shiozaki EN, Chai J, Rigotti DJ, et al. Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell 2003;11:519-27
  • Srinivasula SM, Hegde R, Saleh A, et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 2001;410:112-6
  • Sanna MG, Duckett CS, Richter BW, et al. Selective activation of JNK1 is necessary for the anti-apoptotic activity of hILP. Proc Natl Acad Sci USA 1998;95:6015-20
  • Sanna MG, da Silva CJ, Ducrey O, et al. IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition. Mol Cell Biol 2002;22:1754-66
  • Lewis J, Burstein E, Reffey SB, et al. Uncoupling of the signaling and caspase-inhibitory properties of X-linked inhibitor of apoptosis. J Biol Chem 2004;279:9023-9
  • Hofer-Warbinek R, Schmid JA, Stehlik C, et al. Activation of NF-κB by XIAP, the X chromosome-linked inhibitor of apoptosis, in endothelial cells involves TAK1. J Biol Chem 2000;275:22064-8
  • Lu M, Lin SC, Huang Y, et al. XIAP induces NF-κB activation via the BIR1/TAB1 interaction and BIR1 dimerization. Mol Cell 2007;26:689-702
  • Birkey RS, Wurthner JU, Parks WT, et al. X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-β signaling. J Biol Chem 2001;276:26542-9
  • Carter BZ, Milella M, Tsao T, et al. Regulation and targeting of antiapoptotic XIAP in acute myeloid leukemia. Leukemia 2003;17:2081-9
  • Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003;22:8581-9
  • Uren AG, Wong L, Pakusch M, et al. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol 2000;10:1319-28
  • Beltrami E, Plescia J, Wilkinson JC, et al. Acute ablation of survivin uncovers p53-dependent mitotic checkpoint functions and control of mitochondrial apoptosis. J Biol Chem 2004;279:2077-84
  • Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998;396:580-4
  • Adida C, Crotty PL, McGrath J, et al. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 1998;152:43-9
  • Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997;3:917-21
  • Okada H, Bakal C, Shahinian A, et al. Survivin loss in thymocytes triggers p53-mediated growth arrest and p53-independent cell death. J Exp Med 2004;199:399-410
  • Jiang X, Wilford C, Duensing S, et al. Participation of survivin in mitotic and apoptotic activities of normal and tumor-derived cells. J Cell Biochem 2001;83:342-54
  • Li F, Ackermann EJ, Bennett CF, et al. Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol 1999;1:461-6
  • Liston P, Roy N, Tamai K, et al. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 1996;379:349-53
  • Roy N, Deveraux QL, Takahashi R, et al. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J 1997;16:6914-25
  • Eckelman BP, Salvesen GS. The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 2006;281:3254-60
  • Samuel T, Welsh K, Lober T, et al. Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspases. J Biol Chem 2006;281:1080-90
  • Wang CY, Mayo MW, Korneluk RG, et al. NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 1998;281:1680-3
  • Chen Z, Naito M, Hori S, et al. A human IAP-family gene, apollon, expressed in human brain cancer cells. Biochem Biophys Res Commun 1999;264:847-54
  • Vucic D, Stennicke HR, Pisabarro MT, et al. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol 2000;10:1359-66
  • Kasof GM, Gomes BC. Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem 2001;276:3238-46
  • Ashhab Y, Alian A, Polliack A, et al. Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern. FEBS Lett 2001;495:56-60
  • Lin JH, Deng G, Huang Q, Morser J. KIAP, a novel member of the inhibitor of apoptosis protein family. Biochem Biophys Res Commun 2000;279:820-31
  • Richter BW, Mir SS, Eiben LJ, et al. Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family. Mol Cell Biol 2001;21:4292-301
  • Mirza A, McGuirk M, Hockenberry TN, et al. Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene 2002;21:2613-22
  • Zhou M, Gu L, Li F, et al. DNA damage induces a novel p53-survivin signaling pathway regulating cell cycle and apoptosis in acute lymphoblastic leukemia cells. J Pharmacol Exp Ther 2002;303:124-31
  • Hoffman WH, Biade S, Zilfou JT, et al. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem 2002;277:3247-57
  • Notarbartolo M, Cervello M, Dusonchet L, D'Alessandro N. NAIP-ΔEx10-11: a novel splice variant of the apoptosis inhibitor NAIP differently expressed in drug-sensitive and multidrug-resistant HL60 leukemia cells. Leuk Res 2002;26:857-62
  • Knauer SK, Bier C, Schlag P, et al. The survivin isoform survivin-3B is cytoprotective and can function as a chromosomal passenger complex protein. Cell Cycle 2007;6:1502-9
  • Vaux DL, Silke J. IAPs, RINGs and ubiquitylation. Nat Rev Mol Cell Biol 2005;6:287-97
  • Dan HC, Sun M, Kaneko S, et al. Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem 2004;279:5405-12
  • Shi Y. A conserved tetrapeptide motif: potentiating apoptosis through IAP-binding. Cell Death Differ 2002;9:93-5
  • Shiozaki EN, Shi Y. Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology. Trends Biochem Sci 2004;29:486-94
  • Verhagen AM, Ekert PG, Pakusch M, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000;102:43-53
  • Liu Z, Sun C, Olejniczak ET, et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature 2000;408:1004-8
  • Wu G, Chai J, Suber TL, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature 2000;408:1008-12
  • Srinivasula SM, Datta P, Fan XJ, et al. Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway. J Biol Chem 2000;275:36152-7
  • Hao Y, Sekine K, Kawabata A, et al. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol 2004;6:849-60
  • Hegde R, Srinivasula SM, Zhang Z, et al. Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 2002;277:432-8
  • Martins LM, Iaccarino I, Tenev T, et al. The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem 2002;277:439-44
  • Suzuki Y, Imai Y, Nakayama H, et al. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 2001;8:613-21
  • van LG, van GM, Depuydt B, et al. The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ 2002;9:20-6
  • Vaux DL, Silke J. Mammalian mitochondrial IAP binding proteins. Biochem Biophys Res Commun 2003;304:499-504
  • Verhagen AM, Silke J, Ekert PG, et al. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem 2002;277:445-54
  • Sekine K, Hao Y, Suzuki Y, et al. HtrA2 cleaves Apollon and induces cell death by IAP-binding motif in Apollon-deficient cells. Biochem Biophys Res Commun 2005;330:279-85
  • Liston P, Fong WG, Kelly NL, et al. Identification of XAF1 as an antagonist of XIAP anti-caspase activity. Nat Cell Biol 2001;3:128-33
  • Xia Y, Novak R, Lewis J, et al. Xaf1 can cooperate with TNFα in the induction of apoptosis, independently of interaction with XIAP. Mol Cell Biochem 2006;286:67-76
  • Leaman DW, Chawla-Sarkar M, Vyas K, et al. Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. J Biol Chem 2002;277:28504-11
  • Wang J, Peng Y, Sun YW, et al. All-trans retinoic acid induces XAF1 expression through an interferon regulatory factor-1 element in colon cancer. Gastroenterology 2006;130:747-58
  • Zou B, Chim CS, Zeng H, et al. Correlation between the single-site CpG methylation and expression silencing of the XAF1 gene in human gastric and colon cancers. Gastroenterology 2006;131:1835-43
  • Verhagen AM, Kratina TK, Hawkins CJ, et al. Identification of mammalian mitochondrial proteins that interact with IAPs via N-terminal IAP binding motifs. Cell Death Differ 2007;14:348-57
  • Galvan V, Kurakin AV, Bredesen DE. Interaction of checkpoint kinase 1 and the X-linked inhibitor of apoptosis during mitosis. FEBS Lett 2004;558:57-62
  • Hegde R, Srinivasula SM, Datta P, et al. The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. J Biol Chem 2003;278:38699-706
  • Xing Z, Conway EM, Kang C, Winoto A. Essential role of survivin, an inhibitor of apoptosis protein, in T cell development, maturation, and homeostasis. J Exp Med 2004;199:69-80
  • Fukuda S, Pelus LM. Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34(+) cells by hematopoietic growth factors: implication of survivin expression in normal hematopoiesis. Blood 2001;98:2091-100
  • Leung CG, Xu Y, Mularski B, et al. Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells. J Exp Med 2007;204:1603-11
  • Lopes R, Castro I, Pontes P, et al. Expression profile of survivin in acute leukaemias: the importance of differential splicing. Leukemia 2005;19:1284-6
  • Rigaud S, Fondaneche MC, Lambert N, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature 2006;444:110-4
  • Johnson DE, Gastman BR, Wieckowski E, et al. Inhibitor of apoptosis protein hILP undergoes caspase-mediated cleavage during T lymphocyte apoptosis. Cancer Res 2000;60:1818-23
  • Hasegawa T, Suzuki K, Sakamoto C, et al. Expression of the inhibitor of apoptosis (IAP) family members in human neutrophils: up-regulation of cIAP2 by granulocyte colony-stimulating factor and overexpression of cIAP2 in chronic neutrophilic leukemia. Blood 2003;101:1164-71
  • Vega F, Medeiros LJ. Marginal-zone B-cell lymphoma of extranodal mucosa-associated lymphoid tissue type: molecular genetics provides new insights into pathogenesis. Adv Anat Pathol 2001;8:313-26
  • Dierlamm J, Baens M, Wlodarska I, et al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood 1999;93:3601-9
  • Remstein ED, James CD, Kurtin PJ. Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas. Am J Pathol 2000;156:1183-8
  • Baens M, Maes B, Steyls A, et al. The product of the t(11;18), an API2-MLT fusion, marks nearly half of gastric MALT type lymphomas without large cell proliferation. Am J Pathol 2000;156:1433-9
  • Hosokawa Y. Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma. Apoptosis 2005;10:25-34
  • Izumiyama K, Nakagawa M, Yonezumi M, et al. Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18) (q21;q21) MALT lymphoma. Oncogene 2003;22:8085-92
  • Varfolomeev E, Wayson SM, Dixit VM, et al. The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF-κB activation independently of TRAF1 and TRAF2. J Biol Chem 2006;281:29022-9
  • Hu S, Du MQ, Park SM, et al. cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas. J Clin Invest 2006;116:174-81
  • de Graaf AO, van Krieken JH, Tonnissen E, et al. Expression of C-IAP1, C-IAP2 and survivin discriminates different types of lymphoid malignancies. Br J Haematol 2005;130:852-9
  • Nowak D, Boehrer S, Brieger A, et al. Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. Leuk Lymphoma 2004;45:1429-36
  • Kashkar H, Haefs C, Shin H, et al. XIAP-mediated caspase inhibition in Hodgkin's lymphoma-derived B cells. J Exp Med 2003;198:341-7
  • Kashkar H, Deggerich A, Seeger JM, et al. NF-κB-independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs. Blood 2007;109:3982-8
  • Kashkar H, Seeger JM, Hombach A, et al. XIAP targeting sensitizes Hodgkin lymphoma cells for cytolytic T-cell attack. Blood 2006;108:3434-40
  • Durkop H, Hirsch B, Hahn C, Stein H. cIAP2 is highly expressed in Hodgkin-Reed-Sternberg cells and inhibits apoptosis by interfering with constitutively active caspase-3. J Mol Med 2006;84:132-41
  • Oto OA, Paydas S, Tanriverdi K, et al. Survivin and EPR-1 expression in acute leukemias: Prognostic significance and review of the literature. Leuk Res 2007;31:1495-501
  • Troeger A, Siepermann M, Escherich G, et al. Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia. Haematologica 2007;92:1043-50
  • Nakagawa Y, Yamaguchi S, Hasegawa M, et al. Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia. Leuk Res 2004;28:487-94
  • Romagnoli M, Trichet V, David C, et al. Significant impact of survivin on myeloma cell growth. Leukemia 2007;21:1070-8
  • Wu H, Ma Y, Zhu Y, et al. Expression of BIRC7 protein and mRNA in non-Hodgkin's lymphoma. Leuk Lymphoma 2006;47:1110-6
  • Choi J, Hwang YK, Sung KW, et al. Expression of livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia. Blood 2007;109:471-7
  • Qiuping Z, Jei X, Youxin J, et al. CC chemokine ligand 25 enhances resistance to apoptosis in CD4+ T cells from patients with T-cell lineage acute and chronic lymphocytic leukemia by means of livin activation. Cancer Res 2004;64:7579-87
  • Hess CJ, Berkhof J, Denkers F, et al. Activated intrinsic apoptosis pathway is a key related prognostic parameter in acute myeloid leukemia. J Clin Oncol 2007;25:1209-15
  • Nawata R, Yujiri T, Nakamura Y, et al. MEK kinase 1 mediates the antiapoptotic effect of the Bcr-Abl oncogene through NF-κB activation. Oncogene 2003;22:7774-80
  • Doyle BT, O'Neill AJ, Newsholme P, et al. The loss of IAP expression during HL-60 cell differentiation is caspase-independent. J Leukoc Biol 2002;71:247-54
  • Notarbartolo M, Cervello M, Poma P, et al. Expression of the IAPs in multidrug resistant tumor cells. Oncol Rep 2004;11:133-6
  • Notarbartolo M, Cervello M, Dusonchet L, et al. Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression of P-glycoprotein, Fas and of the novel anti-apoptosis factors IAP (inhibitory of apoptosis proteins). Cancer Lett 2002;180:91-101
  • Tamm I, Richter S, Scholz F, et al. XIAP expression correlates with monocytic differentiation in adult de novo AML: impact on prognosis. Hematol J 2004;5:489-95
  • Tamm I, Kornblau SM, Segall H, et al. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 2000;6:1796-803
  • Tamm I, Richter S, Oltersdorf D, et al. High expression levels of X-linked inhibitor of apoptosis protein and survivin correlate with poor overall survival in childhood de novo acute myeloid leukemia. Clin Cancer Res 2004;10:3737-44
  • Zhang J, Li Y, Shen B. Up-regulation of XIAP by M-CSF is associated with resistance of myeloid leukemia cells to apoptosis. Leukemia 2002;16:2163-5
  • Carter BZ, Kornblau SM, Tsao T, et al. Caspase-independent cell death in AML: caspase inhibition in vitro with pan-caspase inhibitors or in vivo by XIAP or survivin does not affect cell survival or prognosis. Blood 2003;102:4179-86
  • Wagner M, Schmelz K, Wuchter C, et al. In vivo expression of survivin and its splice variant survivin-2B: impact on clinical outcome in acute myeloid leukemia. Int J Cancer 2006;119:1291-7
  • Conte E, Stagno F, Guglielmo P, et al. Survivin expression in chronic myeloid leukemia. Cancer Lett 2005;225:105-10
  • Hernandez-Boluda JC, Bellosillo B, Vela MC, et al. Survivin expression in the progression of chronic myeloid leukemia: a sequential study in 16 patients. Leuk Lymphoma 2005;46:717-22
  • Gianelli U, Fracchiolla NS, Cortelezzi A, et al. Survivin expression in “low-risk” and “high-risk” myelodysplastic syndromes. Ann Hematol 2007;86:185-9
  • Invernizzi R, Travaglino E, Benatti C, et al. Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia. Eur J Haematol 2006;76:494-501
  • Abe S, Yamamoto K, Hasegawa M, et al. Bone marrow cells of myelodysplastic syndromes exhibit significant expression of apollon, livin and ILP-2 with reduction after transformation to overt leukemia. Leuk Res 2005;29:1095-6
  • Yamamoto K, Abe S, Nakagawa Y, et al. Expression of IAP family proteins in myelodysplastic syndromes transforming to overt leukemia. Leuk Res 2004;28:1203-11
  • Nikolovska-Coleska Z, Xu L, Hu Z, et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. J Med Chem 2004;47:2430-40
  • Li L, Thomas RM, Suzuki H, et al. A small molecule Smac mimic potentiates T. Science 2004;305:1471-4
  • Park CM, Sun C, Olejniczak ET, et al. Non-peptidic small molecule inhibitors of XIAP. Bioorg Med Chem Lett 2005;15:771-5
  • Schimmer AD, Welsh K, Pinilla C, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 2004;5:25-35
  • Wu TY, Wagner KW, Bursulaya B, et al. Development and characterization of nonpeptidic small molecule inhibitors of the XIAP/caspase-3 interaction. Chem Biol 2003;10:759-67
  • Wang Z, Cuddy M, Samuel T, et al. Cellular, biochemical, and genetic analysis of mechanism of small molecule IAP inhibitors. J Biol Chem 2004;279:48168-76
  • Carter BZ, Gronda M, Wang Z, et al. Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells. Blood 2005;105:4043-50
  • Oost TK, Sun C, Armstrong RC, et al. Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J Med Chem 2004;47:4417-26
  • Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site. J Med Chem 2004;47:4147-50
  • Kater AP, Dicker F, Mangiola M, et al. Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis. Blood 2005;106:1742-8
  • Cillessen SA, Reed JC, Welsh K, et al. Small-molecule XIAP antagonist restores caspase-9 mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells. Blood 2008;111:369-75
  • Chauhan D, Neri P, Velankar M, et al. Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM). Blood 2007;109:1220-7
  • Petersen SL, Wang L, Yalcin-Chin A, et al. Autocrine TNFα signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell 2007;12:445-56
  • Vince JE, Wong WW, Khan N, et al. IAP antagonists target cIAP1 to induce TNFα-dependent apoptosis. Cell 2007;131:682-93
  • Varfolomeev E, Blankenship JW, Wayson SM, et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-κB activation, and TNFα-dependent apoptosis. Cell 2007;131:669-81
  • Gaither A, Porter D, Yao Y, et al. A Smac mimetic rescue screen reveals roles for inhibitor of apoptosis proteins in tumor necrosis factor-α signaling. Cancer Res 2007;67:11493-8
  • Olie RA, Simoes-Wust AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res 2000;60:2805-9
  • Jansen B, Zangemeister-Wittke U. Antisense therapy for cancer–the time of truth. Lancet Oncol 2002;3:672-83
  • Sasaki H, Sheng Y, Kotsuji F, Tsang BK. Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res 2000;60:5659-66
  • Bilim V, Kasahara T, Hara N, et al. Role of XIAP in the malignant phenotype of transitional cell cancer (TCC) and therapeutic activity of XIAP antisense oligonucleotides against multidrug-resistant TCC in vitro. Int J Cancer 2003;103:29-37
  • McManus DC, Lefebvre CA, Cherton-Horvat G, et al. Loss of XIAP protein expression by RNAi and antisense approaches sensitizes cancer cells to functionally diverse chemotherapeutics. Oncogene 2004;23:8105-17
  • Gordon GJ, Appasani K, Parcells JP, et al. Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma. Carcinogenesis 2002;23:1017-24
  • Cao C, Mu Y, Hallahan DE, Lu B. XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. Oncogene 2004;23:7047-52
  • Lima RT, Martins LM, Guimaraes JE, et al. Chemosensitization effects of XIAP downregulation in K562 leukemia cells. J Chemother 2006;18:98-102
  • Wang X, Wang C, Yan SK, Gao YR. XIAP is upregulated in HL-60 cells cocultured with stromal cells by direct cell contact. Leuk Res 2007;31:1133-7
  • Congmin G, Mu Z, Yihui M, Hanliang L. Survivin–an attractive target for RNAi in non-Hodgkin's lymphoma, Daudi cell line as a model. Leuk Lymphoma 2006;47:1941-8
  • Carter BZ, Mak DH, Schober WD, et al. Regulation of survivin expression through Bcr-Abl/MAPK cascade: targeting survivin overcomes imatinib resistance and increases imatinib sensitivity in imatinib-responsive CML cells. Blood 2006;107:1555-63
  • Ansell SM, Arendt BK, Grote DM, et al. Inhibition of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma. Leukemia 2004;18:616-23
  • Hu Y, Cherton-Horvat G, Dragowska V, et al. Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo. Clin Cancer Res 2003;9:2826-36
  • Lacasse EC, Cherton-Horvat GG, Hewitt KE, et al. Preclinical characterization of AEG35156/GEM 640, a second-generation antisense oligonucleotide targeting X-linked inhibitor of apoptosis. Clin Cancer Res 2006;12:5231-41
  • Available from: www.clinicaltrial.gov
  • Grossman D, Kim PJ, Schechner JS, Altieri DC. Inhibition of melanoma tumor growth in vivo by survivin targeting. Proc Natl Acad Sci USA 2001;98:635-40
  • Schmidt SM, Schag K, Muller MR, et al. Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells. Blood 2003;102:571-6
  • Siegel S, Wagner A, Schmitz N, Zeis M. Induction of antitumour immunity using survivin peptide-pulsed dendritic cells in a murine lymphoma model. Br J Haematol 2003;122:911-4
  • Zeis M, Siegel S, Wagner A, et al. Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells. J Immunol 2003;170:5391-7
  • Arnt CR, Chiorean MV, Heldebrant MP, et al. Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ J Biol Chem 2002;277:44236-43
  • Guo F, Nimmanapalli R, Paranawithana S, et al. Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis. Blood 2002;99:3419-26
  • Ng CP, Bonavida B. X-linked inhibitor of apoptosis (XIAP) blocks Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of prostate cancer cells in the presence of mitochondrial activation: sensitization by overexpression of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pl (Smac/DIABLO). Mol Cancer Ther 2002;1:1051-8
  • Fulda S, Wick W, Weller M, Debatin KM. Smac agonists sensitize for Apo2L/T. Nat Med 2002;8:808-15
  • Yang L, Mashima T, Sato S, et al. Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide. Cancer Res 2003;63:831-7
  • Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design of potent, conformationally constrained Smac mimetics. J Am Chem Soc 2004;126:16686-7
  • Sun H, Nikolovska-Coleska Z, Chen J, et al. Structure-based design, synthesis and biochemical testing of novel and potent Smac peptido-mimetics. Bioorg Med Chem Lett 2005;15:793-7
  • Qi R, Gu J, Zhang Z, et al. Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis. Cancer Gene Ther 2007;14:82-90
  • Jia L, Patwari Y, Kelsey SM, et al. Role of Smac in human leukaemic cell apoptosis and proliferation. Oncogene 2003;22:1589-99
  • Milella M, Kornblau SM, Estrov Z, et al. Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia. J Clin Invest 2001;108:851-9
  • Altieri DC. Targeted therapy by disabling crossroad signaling networks: the survivin paradigm. Mol Cancer Ther 2006;5:478-82
  • Mesri M, Wall NR, Li J, et al. Cancer gene therapy using a survivin mutant adenovirus. J Clin Invest 2001;108:981-90
  • Goldberg AL, Rock K. Not just research tools–proteasome inhibitors offer therapeutic promise. Nat Med 2002;8:338-40
  • Mitsiades CS, Mitsiades N, Poulaki V, et al. Activation of NF-κB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications. Oncogene 2002;21:5673-83
  • Mitsiades N, Mitsiades CS, Richardson PG, et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 2003;101:2377-80
  • Lopes UG, Erhardt P, Yao R, Cooper GM. p53-dependent induction of apoptosis by proteasome inhibitors. J Biol Chem 1997;272:12893-6

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.