1107 Index 14-3-3 108, 349 ff., 470 ff., 500, 529, 764 ff., AGC kinase 464 ff. 950 ff., 1057 agents – targeted 1079 a aging 17AAG (17-allylamino-17-demethoxygeld- – cellular 686 anamycin) 903, 943 ff., 958 f., 1025 – organismic 686 f. A20 108 AHA1 940 aberration AIDS 3, 67 – chromosomal 807 AIF (apoptosis inducing factor) 5, 205 ff., ACAMP, see apoptotic cell-associated 225 ff., 233 ff., 760, 850, 948 ff., 1059 molecular pattern – apoptotic function 238 acetylation 1015 ff. – cancer 249 acid sphingomyelinase (aSMase) 104, 997 f. – DNA fragmentation 246 actinomycin D 854 – down regulation 239 activation-induced cell death (AICD) – expression 234 10, 96 ff. – homolog 237 activin 495, 1099 – isoform 236 ACTR 1017 – release 241 acute myeloid leukemia (AML) 71, 419, – structure 234 917, 1018 AIF-homologous mitochondrion-associated acute promyelocytic leukemia 678, 1017 f. inducer of cell death (AMID), acyl-CoA-binding protein (ACBP) 210 see also p53-responsive gene 3 207, 237 adaptor protein (AP) AIF-like (AIFL) 207, 237 – AP-1 603 Akt, see protein kinase B – AP-2 603 aliphatic acids 1019 – AP-3 603 alkylating agent 799 – AP-4 603 alkylation therapy 842 adenine nucleotide translocator (ANT) alkyllysophospholipids (ALP) 1068 241, 286, 352, 578 alkylphosphocholines 1068 adenomatous polyposis alkyltransferase 799 – coli (APC) 176, 478 Alzheimerls disease 140 – familiarly adenomatous polyposis (FAP) aminopeptidase N (CD13) 112 syndrome 1073 aminophospholipid translocase 586 f. adenovirus amplification 164, 894, 973, 1018 – adenoviral gene transfer 903, 1035 AN-9 1026 – adenoviral vector-based system 852 anaplastic large cell lymphoma 678 – conditionally replicative 1035 androgen receptor (AR) 163 ff. – replication-selective 904 angiogenesis 17, 658, 714, 1064, 1087 f. adenylate kinase 2 (AK2) 209 – angiogenic switch 1090 adriamycin 607, 683, 906 – anti-angiogenic factor 1099 Apoptosis and Cancer Therapy. Edited by K.-M. Debatin and S. Fulda Copyright c 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-31237-4 1108 Index – anti-angiogenic strategy, see inhibitors – MGMT triggered 802 of angiogenesis – modulator 1065 – pro-angiogenic factor 1091 – p53 influence on extrinsic and intrinsic angiopoietin 1095 pathway 519 ff. animal model 1080 – p53-mediated 1054 ankyrin repeat 446 – pathway 757 ff., 891 ff., 947 ff., 1049 ff. Annexin-I 587, 627, 654 – PKB 470 Annexin-V 713 – radiation sensitivity 1062 ansamycin 903 – radiation-induced 587 antennapedia 900 – Raf 497 f. antibody-TNF fusion protein 112 – ras-dependent protection 492 antisense – receptor pathway 850 – RNA technology 337 – regulation of DNA-damage-induced – oligonucleotide 853 apoptosis 273 – therapy 420 – resistance 1057 AP-1 814, 901 – shutdown of ATP-hydrolyzing enzyme Apaf-1, and RNA/protein synthesis 272 see apoptotic protease-activating factor-1 – signaling 4, 997 ff., 1049 ff. APO2L, – signaling kinase 1 (ASK1) 108, 504 see TNF-related apoptosis-inducing ligand – stress-induced 768 Apollon/BRUCE 227, 915 – TNF-induced apoptosis 560 apoptogenic protein 579 – TRAIL 40 apoptosis, see also programmed cell death –UV-C induced 805 3 ff., 156 ff., 282 ff., 382, 558, 658, 682 ff., apoptosis-inducing factor, see AIF 778, 799 ff., 849, 895 ff., 948, 997 ff., 1036, apoptosis-stimulating proteins of p53 1049 ff. (ASPP) 541 – antiapoptotic protein 13, 560 apoptosis signal-regulating kinase-1 – apoptosome 282 ff. (ASK-1) 108, 504, 767, 957 – apoptotic bodies 572 apoptosome 9, 190, 266 ff., 282 ff., 302, 321, – apoptotic cell clearance 625 ff., 648 ff. 609, 766 ff. – apoptotic cell-associated molecular pattern –Apaf-1 5, 266, 288 ff., 850 (ACAMP) 653 – cancer therapy 299 ff. – apoptotic chromatin condenser in the – caspase-9 5, 266 ff., 766 nucleus (ACINUS) 271 – embryonic development 298 – apoptotic threshold 1061 ff., 1079 – physiological regulation 296 – biochemical feature 271 ff. apoptotic protease-activating factor-1/ –Ca2+ 571 ff. apoptosis-promoting factor-1 (Apaf-1) 14, – caspase independent 851 104, 285 ff., 299 ff., 321 ff., 362, 406 ff., 490, – cell rounding and blebbing 272, 572 759 ff., 785 ff., 948 ff., 1074 – ceramide-induced 1054 ff. –Apaf-1-/- cell 957 – dexamethasone-induced 575 –Apaf-1-null mouse 298 – DNA damaging agents 799 ff. –Apaf-2, see cytochrome c – extrinsic pathway 4 ff., 406, 519, 718 – embryonic development 298 – FADD-dependent 1074 – interaction with Bcl-2 proteins 362 – genetics 692 APR, see Noxa – glucocorticoid-induced 574 apurinic/apyrimidinic site (AP site) 823 ff. – hypoxia-induced 778 ff. arachidonic acid (AA) 606, 1072 – internucleosomal degradation of DNA ARF, see p16INK4a/ARF (DNA fragmentation) 271, 320 Artemis 834 – intrinsic pathway 4 f., 346, 406, 520 ff., ARTS 204 718, 758 ASK1, see apoptosis signal-regulating – lucifearse-luciferin-system 718 kinase -1 – machinery 4 ff. ASK1-interacting protein (AIP) 108 – mitochondrial pathway 4, 850, 1024 ASM, see sphingomyelinase Index 1109 ataxia telangiectasia 687, 893 Bax/Bak 41, 104, 325, 346 ff., 363 ff., 502, – mutated protein (ATM) 678, 809 ff., 578 ff., 606, 765 ff., 782 ff., 828, 854, 948 ff. 831 ff., 893 ff. – activation 287, 523 ff. Ataxin-1 481 – adenine nucleotide translocator (ANT) ATF-6 790 352, 578 ATP depletion 110, 1059 – Bcl-2 family protein 1039, 1052 ff. ATR (kinase A-T and Rad3-related protein) – Bok 948 810, 826 ff., 839 – C-terminal tail 326 ATR-interacting protein (ATRIP) 840 –Ca2+ homeostasis 363 Aurora B kinase 429 – cancer 365 autoimmune disease 3, 67 – cleavage 349 autoimmune encephalomyelitis (EAE) 140 – conformation 349 ff. autoimmune lymphoproliferative syndrome – cyclophilin 352 (ALPS) 16, 37 – deregulation 334 autoimmunity 633 –ER 363 autophagic cell death 573 – hexokinase 352 autophagosome 603 – inhibitor 1 protein 576 autophagy 573, 603, 783, 851 – ion channel 352 – chaperone-mediated 603 – localization 363 – macroautophagy 603 – knockout mouse 356 – microautophagy 603 – mechanism 350 avian retrovirus 1039 – mitochondrial death pathway 1066 Axin 478 – mitochondrial pore 352 – mutation 14, 365 b – N-Bak 364 B cell 673 – oligomerization 326, 349 f. B cell lymphoma 14, 40, 419, 683, 762, 1018, – outer mitochondrial membrane 1058 1027 – p53-mediated upregulation 521, 901 – Bcl-2 overexpression 14 – proapoptotic 892 B chronic lymphocytic leukemia cell – redundancy 350 (B-CLL) 292 – splice variant 364 bacteria 998 – therapeutic opportunity 366 baculovirus IAP repeat (BIR) 198 ff., 223, – three-dimensional structure 353 407 ff., 427, 913 ff. – translocation 349 – domain 405, 878 ff., 918 ff. – voltage-dependent anion channel (VDAC) – domain antagonist 881 f. 352, 578 – second BIR domain (BIR2) 223, 918 ff. Bbc3, see Puma – Smac-binding pocket 925 Bcl-2 187, 318 ff., 330 ff., 346 ff., 382 ff., – small-molecule BIR2 antagonist 924 ff. 407 ff., 490 ff., 585, 678 ff., 758 ff., 850 ff., – small-molecule BIR3 antagonist 920 ff. 947 ff. – third BIR domain (BIR3) 223, 918 ff. – antiapoptotic protein 4, 41, 322 ff., 892, Bad 328, 470 ff., 499 f., 578, 762 ff., 782, 680 ff., 1063 ff. 854, 950 ff. – apoptosis 4, 40 –14-3-3 353, 470 – autophagy 573 – Bcl-2 family 1052 – Bax ratio 330 – heterodimerization 330 – BH3-only proteins 41, 379, 525 – phosphorylation 353 – cell death 572 – proapoptotic 1025, 1057 – cell survival 583 Bag (Bcl-2 interacting protein) 500, 939 ff., – family 758 ff., 783, 892, 947 ff., 1038 f., 956 1052 BAP (Bcl-2-associated protein) 576 f. – homology (BH) domain 8, 286, 322 ff., base excision repair (BER) 799 ff., 823 ff. 348 ff., 383, 762, 947 basic helix-loop-helix (bHLH)-PAS – interacting protein (Bag) 500, 939 ff., 956 transcription factor family 781 – interaction 356 1110 Index – Noxa 379 – regulation 357 – outer mitochondrial membrane (OMM) – splice variant 364 integrity 225 – structure 355 – overexpression 240, 323 ff., 490, 585, 614, – targeting 355 685, 1058 ff., 1074 – therapeutic opportunity 366 – p53 influence 520 ff. – truncated (tBid) 41, 476, 578, 764, 1052 f. – proapoptotic protein 4, 41, 241, 892 – ubiquitination 358 – prosurvival 322 ff., 759 Bik (Bcl-2-interacting killer) 762, 1039 –Puma 379 Bim 327 f., 364, 392, 501, 762 ff., 951, 1052 – targeted expression 1053 – BimEL 762 Bcl-2-associated protein, see BAP biological modifier 691 Bcl-2-interacting killer, see Bik bioluminescence imaging 688 f., 709 f. Bcl-3 446 BIP 955 Bcl-W 325, 1052 BIR, see baculovirus IAP repeat Bcl-XL 286, 325 ff., 350, 503, 583, 759 ff., BL1521 1020 854, 949, 1025, 1052 ff. Bloom’s syndrome (BS) protein (BLM) 836 ff. – three-dimensional structure 338 Bmf 328, 763 Bcl-XS 764 BNip3 762, 783 f. BCR-ABL 672 ff., 905, 1025 – BNip3-like (BNip3L) 783 f. behacizumab 686 Bok 764, 948 benzamides 1019 bone marrow transplantation (BMT) 71 benzoquinone 903 bone morphogenetic protein (BMP) 494 Bergerat fold 939 ff. bortezomib (PS-341) 1025, 1075 betulinic acid 1067 ff. breast cancer 419, 588 BH1 286, 322 ff., 348 ff., 383, 947 – BRCA1 835 ff., 1018 BH1-3 (multidomain) group 758 ff. – BRCA2 835 ff. BH2 286, 322 ff., 348 ff., 383, 947 Burkitt’s lymphoma 672 BH3 8, 286, 322 ff., 348 ff., 383, 762, 783, 947 butyric acid 1026 – peptide 854 bystander cell 686 – protein 947 f. – three-dimensional structure 353 c BH3 mimetic 338 C225 (Erbituxr, cetuximab) 1050, 1069 BH3-containing protein 470, 787 C-reactive protein 653 BH3-only proteins 187, 287, 327 ff., 353, C-terminal modulator protein (CTMP) 469 379 ff., 501, 578, 758 ff., 854 Ca2+ 1054 ff. – post-translational modification 353 – compartmentalization 573 – regulation 328 – ER-dependent release 244, 790, 1073 BH4 286, 322 ff., 348 ff., 383, 947 – extrusion 573 Bid (BH3-interacting domain) 104, 270 f., – homeostasis 571, 588 328, 346 ff., 360 ff., 584, 606, 762 ff., 782, – hotspot 577 851, 949 ff., 1038, 1052 – overload 572 ff. – bid-deficient mouse 358 – storage 573 ff. – C-terminal (tcBid) 360 – store-operated influx 588 – cancer 365 CAD, see caspase-activated DNase – cardiolipin 361 Caenorhabditis elegans 240, 317 ff., 633, – cathepsin 358 692, 945 – cleavage 354 ff., 1037 calcineurin 578 ff.