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 -associated 225 ff., 233 ff., 760, 850, 948 ff., 1059 molecular pattern – apoptotic function 238 acetylation 1015 ff. – 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 (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 (ACBP) 210 see also p53-responsive 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 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. -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 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 – 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 – 356 – microautophagy 603 – mechanism 350 avian 1039 – mitochondrial death pathway 1066 Axin 478 – mitochondrial pore 352 – mutation 14, 365 b – N-Bak 364 673 – 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 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. – cytochrome c release 360 f. calpain 582 ff., 851 –ER 363 calpastatin 583 – granzyme B 358 cancer 3 ff., 551 ff., 852, 1017 f. – HIF-1 359 – AIF 249 – lipid transport 361 – anticancer drugs 895, 1014 ff. – N-myristoylation 358 – antiapoptotic protein 13 – phosphorylation 358 – -based approach 671 Index 1111

– c-FLIP 140 caspase-3 42, 223, 275 ff., 294, 406 ff., 583 f., – hallmark trait 946 758 f. , 850, 913 ff., 926, 948 ff. – Hsp90 941 – activity 718 – hypoxia 777 ff. – cleavage site (DEVD) 718 – immune surveillance 62, 142 caspase-4 575 – immunotherapy 434 caspase-6 759 – mouse model 671 ff. caspase-7 42, 223, 275 f., 294, 583, 759, 913, – susceptibility 822 926, 949 – therapy 44 ff., 228, 282 ff., 299 ff., 318, caspase-8 99 ff., 123 ff., 263 ff., 406 ff., 576 ff., 335 ff., 639, 997 ff. 609, 758 ff., 805, 850, 913, 949 ff., 1052 f. – treatment sensitivity 681 – gene methylation 278 – vaccination 433 – heterotetramer 100 cancer drug discovery – loss in small cell carcinoma 278 – rational design 319 – p43 fragment 100 carcinoembryonic (CEA) 112 caspase-9 42, 190 ff., 223, 263 ff., 293 ff., cardiolipin 189 ff., 580 321 ff., 406 ff., 432, 471, 491, 583, 609, – peroxidation 580 758 f., 785 ff., 850, 913 ff., 948 f., 1074 CARMA-1/CARD11 pathway 127 – procaspase-9 1052 caspases (cysteine-dependent, aspartate- caspase-10 38, 123, 758 specific proteases) 36, 260 ff., 320 ff., caspase-11 324 407 ff., 572, 758 ff., 850, 864 ff., 947 ff. caspase-12 324, 406 ff. – activation 265 ff., 491, 865 ff. – cluster 276 – AIF 243 caspase-activated DNase (CAD) 5, 271, 759 ff. – amplification 164 caspase-activator 876 ff. – cancer 277 f. – immunocaspase-3 876 – cascade 268 – immunocaspase-6 876 – catalytic mechanism 866 ff. – inducible caspase-9 (iCasp9) 876 – cell death 583 –MX-2060 878 – death effector domain (DED) 263 –MX-2167 878 – effector 4 ff., 864 – PETCM 877 – executioner 263 ff., 321 – RGD peptides 877 – frequency of mutation in cancer 277 caspase-inhibitors 869 ff., 1022 – inactivation 277, 491 – chemistry 871 ff. – induced-proximity model 38, 294 – reagents 869 ff. – inflammatory 864 – reversible/irreversible 871 ff. – inhibiting kinase 491 – warhead 871 ff. – initiator 4 ff., 31, 262, 321, 758, 864 caspase activation 265 ff. – NIRF-based imaging 718 – apoptosome-mediated 266 – null mouse 273 ff. – anticancer therapy 278 – physiological role 273 ff. – caspase adaptor proteins 266 – procaspase 575, 948 ff., 1052 – catalytic pocket 265 – prodomain 262 – death receptor-mediated 268 – proteasome 1075 – enforced dimerization 266 – recruitment domain (CARD) 127, 263, – granzyme B-mediated 269 288 ff., 758, 865, 916 – index of zymogenicity 266 – role as tumor suppressor 277 – inflammasome 269 – specificity 264 – interdomain processing 265 – substrate 270 ff., 913 – mitochondrial pathway 850 – substrate binding 868 – receptor pathway 850 – zymogen 4,168, 262 ff., 913 – removal of prodomain 265 caspase-1, see also CED-3 276, 283, 324, – TRAIL DISC 38 690, 864 ff. – viral of caspase expression – inhibitor 871 ff. construct 278 caspase-2 274, 324, 362 f., 758, 813, 850 b-catenin 477, 685 1112 Index

cathepsin protease 600 ff., 851 – cell-of-origin 672 – cathepsin B 111, 606 ff., 717 – xenogeneic origin 674 – cathepsin D 104, 606 ff. 474 f., 558, 682 – cathepsin G 611 – arrest 528 f., 766, 901 f. – cathepsin H 611 – progression 473, 1023 f. – cathepsin K 611 cell death 572 – cathepsin L 606 ff. – activation induced (AICD) 10, 124 – cathepsin V 611 – caspase-independent 302 f. CBHA (M-carboxycinnamic acid – interphase 1051 bishydroxamide) 1020 ff. – machinery 470 CBP, see CREB – regulation 225 CBP-associated factor (CAF) 1017 – reproductive 1051 CCAAT-binding transcription factor (CTF) – rheostat model 330 541 cell death defective (CED) 260, 633 ff. CCI-779 987, 1040 – CED-1/CD91/LRP/SREC 633, 651 CCT018159 944 – CED-2/CrkII 633 ff., 651 CD3 769 – CED-3/caspase-1 260, 283, 317 CD4 62 – CED-4 283 ff., 317 ff. CD5 1003 – CED-5/Dock180 633 ff., 651 CD8 62, 127 – CED-6/GULP 633, 651 – helpless 62 – CED-7/ABCA1 633, 651 CD14 653 f., 1003 – CED-9 283 ff., 317 ff. CD20 998 ff. – CED-10/Rac 635 CD28 1003 – CED-12/ELMO 635, 651 CD30 104 – CED-13 327 CD31/PECAM-1 587, 631, 654 cellular FLICE-like inhibitory protein CD36 653 (c-FLIP) 39, 100 ff., 120 ff., 142, 1063 CD40 104, 1003 – cancer 140 CD43 654 – disease 130 CD47 655 – function 123 f. CD68/macrosialin 653 – regulation of expression 129 CD91/LRP/SREC/CED-1 633, 651 ff. – structure 121 CD95 (APO-1/Fas) 32 , 354, 383, 759, cellular inhibitor of apoptosis (c-IAP), 850, 948, 998 ff., 1054 f. see inhibitor of apoptosis proteins – mutation 14 f. cellular senescence 685 ff. – signaling 8 f. cellular stressor 758 – tumor suppressor 16 ceramidase CD95 ligand (CD95L) 10 f., 94 ff., 581, – acid 610 851, 1035 ff., 1063 ceramide 110, 579, 605 ff., 997 ff., 1054 ff. – mutation 14 f. – de novo generation 1055 CD95/CD95L system 7 ff. – liberator 1068 – cancer therapy 17 ff. – signaling 997 ff. – tumor progression 19 f. – synthase (CS) 1055 ff. CDB3 900 ff. cetuximab (Erbituxr, C225) cdc2 475 1050, 1069 f. cdc25C 787 CGH, CDE/CHR box 428 see comparative genomic hybridization celecoxib 982 f., 1073 ff. CHAP1 1025 cell CHAP31 1025 – allogeneic origin 674 chaperone 789, 900 – cell detachment 758 – chemical 902 ff. – cell division 429 – co-chaperone 938 ff., 953 – cell injury 571 – cycle 938 ff. – cell survival 492 – molecular chaperone 933 ff. Index 1113 checkpoint kinase 894 Crohnls disease 96 – Chk1 539 CT, see X-ray computed tomography – Chk2 893 f. curcumin 456 chemoresistance 333, 849 CYC202 896 chemosensitivity 682 ff. cyclic peptides 1019 683, 849, 892 ff. cyclins 1075 – chemotherapeutic agent 332, 831 ff. – cyclin D1 1022 chimeric tumor suppressor (CTS)-1 1035 – cyclin-dependent kinase (CDK) 538, 555 f., CHIP 940 ff. 896, 953 cholesterol 1002 cyclodextrin 1002 chromatin 853 cyclophilin D 286, 578 – condensation 1052 cyclooxygenase-2 (COX-2) 1073 f. – structure 1014 f. – inhibitors (coxibs) 1073 ff. chromosomal engineering 691 cyclophosphamide 683 chronic myeloid leukemia (CML) 71, cyclosporin A 579 672 ff., 905 CypA 247 CI994 1020 cystatin B 611 ciprofloxacin 605 cysteine-rich domain (CRD) 94 cisplatin 588, 902 ff. cytochrome c (Apaf-2) 190 ff., 227, 244, client protein addiction 945 321 ff., 347 ff., 406 ff., 578, 609, 948 ff. clinical trial 672, 903, 987 f., 1026 f., – apoptosis 4 f., 785 1035 ff. – apoptosome formation 285 ff. – biological effective dose (BED) 989 – release 41, 286, 360 f., 577 ff., 759 ff., – prevention 989 850, 1052 – surrogate tissue 989 cytochrome P450 943 – therapeutic index 990 cytokinesis 429 clonogenicity 1061 cytoplasmic dynein intermediate chain clustering 1005, 1058 (CD-IC) 273 CNK1 493 cytoplasmic stress granule 248 Cockayne syndrome (CS) 806, 827, 842 cytostatic drug 905 – protein 827 f. cytotoxic drug treatment 335, 998 collectin 653 cytotoxic T lymphocyte (CTL) 764 colon cancer 685 cytotoxicity 672, 778 colony formation 1060 comparative genomic hybridization (CGH) d 692 D-21266 (perifosiner, octadecyl-(N,N)-dimethyl- complement receptor (CR) 629 piperidinio-4-yl)-phosphate) 983, 1069 concanavalin A (Con A) 451 damage concanavalin A-induced liver injury 451 – normal tissue 1077 condensation – radiation-induced 1076 – cytoplasmic 572 DARK 291 ff. – nuclear 572 Daxx 540, 767, 809 COP9 signalosome (CSN) 827 death decision 757 ff. CoREST 1017 death domain (DD) 6, 95, 759, 865, 916 COX, see cyclooxygenase-2 death effector domain (DED) 7, 99 ff., 758, coxibs 1073 ff. 865, 916 CP-31398 901 ff., 1036 death ligand 10 f. CRD, see cysteine-rich domain death receptor (DR) 4 f., 95 ff., 758 ff., 808, Cre 676 ff., 689 850, 863, 1041 f., 1053 CREB (cyclic AMP response element-binding – DR3 95 ff. protein) 272, 1017 – DR4 1041 – CREB-binding protein (CBP)/p300 539, – DR5 901, 926, 998, 1041, 1066 788, 1017 – ligand 5 crm-A 1042 – mediated apoptosis 274 1114 Index

– pathway 1065 ff. DNA replication fork 822 ff., 839 ff. – subfamily 32 DNA-dependent protein kinase (DNA-PK) 466 death-inducing signaling complex (DISC) – catalytic subunit (DNA-PKcs) 833 31, 100, 123, 406, 760 ff., 853, 865 donlt eat me signal 63 decoy receptor (DcR) doxorubicin 682, 902, 1000 ff. – DcR1 1041 DR, see death receptor – DcR2 1041 Drp-1 578 – DcR3 853 DRONC 263, 296 degenerative disease 3 Drosophila deguelin 981 – cytochrome c 195 deleted in colorectal cancer (DCC) 159 ff. – RHG protein 921 deletion 1018 drug dependence receptor 156 ff. – molecularly targeted 705 Deterin 431 DT-diaphorase (NQO1) 943 f. developmental death 998 dynein 763 DFF45 271 diacylglycerol (DAG) 1072 e DIAP, see inhibitor of apoptosis proteins E1B55K 904 discodermolide 608 E2F transcription factor 539, 552 f., 787, 1022 17DMAG (17-dimethylaminoethylamino- E3 ubiquitin ligase 44, 405 ff., 478, 540, 784, 17-demethoxygeldanamycin) 943 f. 827 ff., 893 f., 916 ff., 940 ff. DNA – TNF receptor-associated 418 – damage 359, 779, 891 f., 1054, 1077 E6AP 893 – end-joining 681 eat me signal 626 ff. – fragmentation 246, 271, 320, 574, 759ff.,850 ecdysone 677 – interstrand DNA crosslink (ICL) 832 EF5 779 – single strand annealing (SSA) 831 ff. EGFR 112, 973, 1040, 1069 – surveillance mechanism 822 ff. – inhibitors 1078 f. DNA base – signaling 1069 – alkylation 823 f. Egl-1 287, 317 ff. – deamination 822 ff. eIF, see eukaryotic translation initiation factor – oxidation 823 ff. ellipticine 908 DNA damage-induced cell death (DDID) 799 embelin 855, 881 DNA double-stranded break (DSB) 681, embryonic development 298 807 f., 822, 841, 1054 endonuclease 5, 574 ff. – nonhomologous end-joining (NHEJ) – EndoG 208 ff., 226 ff., 246, 760, 948 823 ff., 839 ff. endocytosis 601 – repair 831 ff. – early endosome 601 – surveillance 835 ff. – endocytic carrier vesicle (ECV) 602 DNA microarray 729 ff. – endocytic recycling compartment (ERC) – data analysis 742 601 f. – cancer diagnosis 744 – late endosome 602 – clinical oncology 729 – receptor-mediated 601 – data analysis 742 – sorting endosome 601 f. – experimental design 741 ff. endoplasmatic reticulum (ER) 244, 406, – kinetics 731 571 ff., 1053 ff., 1073 – platform for expression profiling 736 – overload response (EOR) 575 – principle 729 – stress 575, 588, 786 ff. – sample collection 740 engulfment synapse 626 ff. DNA polymerase b (Polb) 824 f. ephrins 1097 DNA repair 242, 687, 799, 822 ff., 1022, 1054 epigenetic – deficient cell line 800 – change 853 – homologous recombination (HR) 822 ff., – mechanism 1015 842 epothilone B 608 Index 1115 erbB flavopiridol 1025 – erbB1/epidermal growth factor receptor, FLICE-inhibitory protein (FLIP)/FLAME-1/ see also EGFR 112, 973, 1040, 1069 I-FLICE/Casper/CFLAR/CASH/MRIT/ – erbB2/HER2 973, 1022 ff. CLARP/Ursupin, see also caspase-8 – erbB3/HER3 973 7 ff., 121, 853, 1075 – erbB4/HER4 973 – cellular (c-FLIP) 1063 r Erbitux (C225/cetuximab) 1050, 1069 – viral (v-FLIP) 121 ERCC1-XPF 827 ff. flox 679 ERK kinase, see mitogen-activated protein fludarabine 1025 kinases and MEK 5-fluorouracil (5-FU) 902 ff., 1025 erlotinib (OSI-774, tarcevar) 1069 fluorescence imaging 688 f., 711 ff. erythropoietin 1064 – autofluorescence 711 ethylnitrosourea (ENU) mutagenesis 691 – electromagnetic spectrum 711 etoposide 605 ff., 760 – fluorochrome 690, 718 ETS family 503 – molecular beacon 711 eukaryotic translation initiation factor – near-IR fluorescent probe (NIRF) 711 ff. (eIF) – red-shifted fluorescent protein 711 – eIF-2a 272, 790 – semiconductor nanocrystals – eIF-2a kinase (PKR)-like ER kinase (quantum dots, qdots) 711 (PERK) 790 forebrain overgrowth (fog) 192, 298 – eIF-4B 272 Forkhead box class O transcription factors – eIF-4E 412 (FOXO) 471 ff., 950 f., 1063 – eIF-4G 272 Fos European Organization for Research – c-Fos 814 and Treatment of Cancer (EORTC) Frizzled membrane receptor 477 1034 fumonisin B1 1058 extracellular signal-regulated protein kinase, see mitogen-activated protein g kinases and MEK G3139 (Oblimersenr) 1038 GADD45 901 f GADD45b 108 FADD, see FAS-associated Death Domain gadolinium 712 – FADD-like interleukin (IL)-1-b-converting gain-of-function mutation 552 enzyme (FLICE) 7 gancyclovir (GCV) 806 FAM-VAD 167 GAP, see GTPase-activating protein FAN, see Sphingomyelinase gastric carcinoma 419 Fanconi anemia (FA) 832 GCN5 1017 – protein 832 ff. gefitinib (ZD1839, Iressar) 1040, 1069 ff. FAP, see adenomatous polyposis geldanamycin (GA) 902, 935 ff., 951 ff. farnesyltransferase 682 – 17AAG (17-allylamino-17-demethoxy- FAS, see CD95 geldanamycin) 943 ff., 958 f. – FAS-associated Death Domain/Mort-1 – 17DMAG (FADD) 7, 37, 99 ff., 759 f., 809, 900, (17-dimethylaminoethylamino- 1005 f. 17-demethoxygeldanamycin) 943 f. –FasL (Fas ligand) 614, 759, 808, 951 gelsolin 272 FcgRII 1003 gene ferritin heavy chain (FHC) 110 – adenoviral gene transfer 1035 [18F]FHBG 713 – amplification 894 fibroblast – gene-to- analysis 675 – fibroblast activation protein (FAP) 112 – 675 – fibroblast growth factor (FGF) 1096 – genetic lesion 682 filipin 1002 – knockdown 680 find me signal 632 – therapy 53, 903 ff. FK228 1020 ff. – transfer 903 1116 Index

genistein 588 h H2AX 840

– maintenance 687 H2O2 605 ff. – genome-based comparative analysis 692 halenaquinone 981 – genomic instability 778 hamartin 467 genotoxic agent 799 harlequin (hq) mouse 206, 247 genotoxic stress 760, 799 – AIF 206 genotype HBXIP 432 – compound 678 HDM-2 (human double minute) 1035 f. GHKL family 939 ff. heat shock 758 ff. ginseng extract 456 – element 936 ff. Gleevecr (Imatinib, STI571) 1039 f. – HSF-1 (heat shock transcription factor-1) 936 glial cell line-derived neutrotrophic factor heat shock protein (Hsp) 762 ff., (GDNF) 162 ff. – Hsc70 603, 944, 955 ff. glioma 852, 1033 ff. – Hsp27 768 f., 954 ff. – glioblastoma 419, 685, 1033 ff. – Hsp40 765, 939 ff. – oligodendroglioma 1037 – Hsp70 245, 608 ff., 765 ff., 939 ff., 955 ff. glucocorticoid 657 – Hsp72 955 ff. glucose – Hsp75/TRAP1 934 ff. – metabolism 475 – Hsp90 110, 434, 764 ff., 903, 933 ff., 959, – deprivation 1064 968, 1024 f. glucose-regulated protein (GRP) HECT-type E3 ubiquitin ligase Itch 540 – GRP58 789 Helicobacter pylori 419 – GRP75 955 hemangiogenesis 1088 ff. – GRP78 789, 955 – mechanism 1091 – GRP94 789, 934 ff. – molecule 1092 ff. – GRP170 789 hematopoietic transplantation GLUT-1 502, 1064 (HSCT) 70 glutathione 769 1018 glycogen synthase kinase GSK-3 476 ff. Her2/neu 770, 973 glycogen-associated protein phosphatase-1 – caspase3 coupled anti-HER2 antibody 278 476 herbimycin A 942 glycolytic pathway 502, 1064 herceptin 876 P-glycoprotein 943 hereditary nonpolyposis colorectal cancer

b2-glycoprotein-I (b2-GPI) 627 (HNPCC) 802, 828, 842 glycosylase 823 ff. herpes simplex thymidine kinase graft-versus-host disease (GVHD) 687 (HSV1-tk) 713 ff. graft-versus tumor (GVT) effect 687 hexokinase 475, 579 granzyme B 358, 583, 758 ff. HIAP, see inhibitor of apoptosis proteins GRASP65 272 Hid 414 GRB2 HIF, see hypoxia-inducible factor green fluorescent protein (GFP) 689 f. Hirschsprung-associated mutations 170 green tea extract 456 histone 1014 Grim 414 – deacetylase inhibitor 853, 1014 ff. growth arrest-specific 6 (Gas-6) 627 – deacetylation 853, 1016 growth factor receptor 973 –HAT (histone acetyl-transferase) 1015 ff. – mutation 973 – HDAC (histone deacetylase) 787, 1015 ff. – overexpression 973 – HDAC1 1017 growth factor withdrawal 758 – HDAC6 1023 GRP, see glucose-regulated protein – nonhistone protein substrates of HDAC GSPT1/eRF3 415 ff. 1023 GTPase-activating protein (GAP) p120RasGAP HIV 67 467, 493 Hodgkin’s lymphoma 917 guanine nucleotide exchange factor (GEF) 493 – non-Hodkin’s lymphoma 918, 1018 Index 1117

Holliday junction 832 ff. – hypoxic selection 1065 homeodomain-interacting protein kinase – p53 786 (HIPK2) 539 hypoxia-inducible factor (HIF) 502, 658, 770, homologous recombination (HR) 675, 777 ff., 1064, 1094 822 ff., 842 – response element 781 homologous to the E6-associated protein C-terminus (HECT) 540 i HS1-associated protein X-1 (HAX-1) 226 IAP-binding motif (IBM) 881 Hsp70 245, 608 ff., 768 f., 939 ff., 955 ff. – peptides 200 ff. – antiapoptotic function 956 IC486068 981 – function 955 ICAM-3 654 – inhibitor 959 IDN-1965 874 ff. – overexpression 958 IDN-6556 874 ff. – structure 955 IkB 44, 446, 504, 1075 f. Hsp72 955 ff. –IkBa 446 – induction 958 –IkBb 446 Hsp90 110, 434, 764 ff., 903, 933 ff., 968, –IkBE 446 1024 f. –IkBg 446 –ATPase 934 ff. IkB kinase (IKK) – cancer 941 – complex 446, 472, 491 ff., 769, 951 f. – C. elegans 945 – IKK inhibitor 456 – chaperone cycle 938 ff. – IKK subunit 446 – client protein 936 ff. – pathway 1063 – function 934 ff. IL, see interleukin – heterodimer 935 ILP, see inhibitor of apoptosis proteins – homodimer 935 imaging, see molecular imaging – Hsp90a 934 ff. Imatinib (Gleevecr, STI571) 1025, 1039 f. – Hsp90b 934 ff. immortalization 613 – Hsp90N 934 ff. immunopathology 67 – inhibitor 935 ff., 959 immunosurveillance 62, 142, 674, 686 – isoform expression and regulation 936 implantation – monorden (Monosporium bonorden) 941 – ectopic 674 – oligomerization 935 inflammasome 864 – structure 934 ff. inflammation-associated cancer 454 HtpG 934 – colitis-associated cancer (CAC) 453 HtrA family 201 – Mdr2 knockout mouse 454 – cancer therapy 228 inhibitor – cell death regulation 225 – small-molecule 913 ff. – HtrA2/OMI 4, 42, 201 ff., 222 ff., 294, inhibitor of CAD (ICAD) 271, 759 ff. 414, 850, 865 ff., 914 inhibitors of angiogenesis 1091 ff. – mutant mouse 227 – endogenous 1099 – structure 224 – nonendogenous 1100 human papilloma virus (HPV) 893 inhibitor of apoptosis proteins (IAP) 44, 168, human telomerase 197, 427, 405 ff., 491, 854, 878 ff., 913 ff., (hTERT) 892 948 ff., 1036, 1055 ff. Huntingtin 480 f. – antiapoptotic 1076 hydroxamates 1019 –Apollon/Bruce/BIRC6 915 hypoxia 769 f., 777 ff., 1026, 1064 – baculoviral IAP repeat (BIR) domain – Bad 782 913 – Bax 782 – Drosophila melanogaster (DIAP1) 296 – Bid 782 – drug targeting 878 ff. – BNip3 783 f. – fusion protein c-IAP2-MALT1 882 – BNip3-like (BNip3L) 783 f. – HIAP1/c-IAP2/MIHC/BIRC3 96 ff., 223, –ERstress 790 411 ff., 770, 854, 881 ff., 915 ff. 1118 Index

– HIAP2/c-IAP1/MIHB/BIRC2 96 ff., 223, c-Jun N-terminal kinase (JNK) 37, 93 ff., 450, 411 ff., 854, 881 ff., 915 ff. 499 ff., 610, 760 ff., 809, 952 ff., 1057 ff. – ILP-2/Ts-IAP/BIRC8 915 – JNK pathway 901, 915 – inhibitor 871 f. – JNK-derived BID (jBID) 109 – livin/ML-IAP/BIRC7 854, 882 f., 915 ff. – JNK/SAPK pathway 1068 – mechanism of caspase inhibition 881 – JNK1 916 ff. – neural IAP (NAIP/BIRC1) 505, 915 ff. – sustained JNK activity 450 – structure and function 914 ff. JunD 107 – survivin/TIAP/BIRC5 915 – XIAP/ILP-1/MIHA/BIRC4 915 k inhibitory proteins IkB, see IkB KF25706 943 inner mitochondrial membrane (IMM) KF58333 943 286, 578 KILLER 901

inositol 1,4,5-trisphosphate (IP3) 1072 kinase inhibitor 856 – receptor (IP3R) 194, 575 ff. kinase suppressor of Raf (KSR) 494, 1057 insulin kinetics, see microspot kinetics – insulin-like growth factor (IGF)-1 kinetochore 429 receptor 892, 1022 knockin lesion 679 – receptor substrates (IRS) 463 Knudson hypothesis 679 integrin family 162, 629, 653, 1098 Ku70 811, 833

– aVb3 717 Ku80 811, 833 ff. – integrin-linked kinase (ILK) 469 intensity-modulated radiation therapy l (IMRT) 1050 lactacystin 940 interferon (IFN) 64 f., 656 lactat dehydrogenase (LDH) 502 – inducible 677 LAMP-2a 603 interleukin LAQ824 1020 ff. – IL-1 605 LAZ3 1018 – IL-1b 864 ff. LBH589A 1027 – IL-1b-converting enzyme (ICE), see also lesion-to-phenotype relationship 678 caspase-1 283 L-leucyl-L-leucine methyl ester 605 – IL-1 receptor 1003 leukemia 683, 852, 918, 1017 – IL-1 receptor-associated kinase (IRAK) 494 – acute myeloid leukemia (AML) 71, 419, – IL-4 657 917, 1018 – IL-6 receptor signaling cascade 1022 – acute promyelocytic leukemia 678, 1018 f. – IL-10 655 ff. – chronic myeloid leukemia (CML) 71, – IL-13 657 672 ff., 905 – IL-18 864 ff. – promyelocytic leukemia protein (PML) 540 internal ribosome entry site (IRES) 413 f., LFA-1 1003 545 f., 770 life decision 757 ff. internucleosomal degradation of DNA 271, Li-Fraumeni syndrome 379 f., 678, 893 320 lipid raft 1058 intra-lysosomal iron 610 Listeria infection 68 ionizing radiation 823 ff., 841 livin, see inhibitor of apoptosis proteins Iressar (gefitinib, ZD1839) 1040, 1069 LKB1 467 g-irradiation 849, 998 ff. loss of heterozygosity (LOH) 679, 835, 853, isatin derivative 871 1018 isolated limb perfusion (ILP) 112 loss-of-function – lesion 679 j – mutation 552 Jafrac2 414 low-affinity nerve growth factor receptor Janus protein kinase (JAK) 65, 491 (p75NGFR)95 – JAK/STAT cascade 1063 LOX-1 653 c-Jun 478 LPC 632 Index 1119

LPS 656 mammalian target of rapamycin (mTOR) luciferase 688 f., 708 467, 685 luciferase-luciferin system 710 ff. – activation 973 –ATP-dependent firefly 710 – clinical trial 987 – MAPK kinase pathway 716 – inhibitor 986 f. – p53-luciferase protein 715 – PI3K/Akt/mTOR pathway 966 ff. – Renilla 710 f. – rapamycin 986 – scattering property 710 – translation 969 – two-dimensional imaging dataset 710 manganese superoxide dismutase (MnSOD) LY294002 977 ff. 110, 1075 lymphangiogenesis 1089 mannose 6-phosphate receptor (MPR) 601 – human 1103 – pathway 602 lymphoma 681 ff., 1017 mannose binding lectin 653 – anaplastic large cell lymphoma 678 MAP kinases, see mitogen-activated protein –Bcell lymphoma 14, 40, 419, 683, 762, kinase 1018, 1027 matrix dehydrogenase 578 –Burkitt’s lymphoma 672 matrix-metalloprotease (MMP) 1099 f. – Em-myc 684 – MMP-2 717 – Hodgkin’s lymphoma 917 Max 272 – mucosa-associated lymphoid tissue Mcl-1 325 ff., 854 (MALT) 13, 419 Mdm2 (murine double minute) 474, 526 ff., – non-Hodkin’s lymphoma 918, 1018 540, 784 ff., 893 ff., 951, 1075 –Tcell lymphoma 1025 ff. – human homolog 1035 f. lymphotoxin (LT) MDR1, see multidrug resistance gene –LT-a 94 medulloblastoma 419 –LT-bR 111 meiosis 822 ff. lysosomal membrane permeabilization MEK (MAPKK), see also mitogen-activated (LMP) 605 ff. protein kinase 493 ff. – TNF-induced 608 ff. – ERK1/2 1063 lysosome 599 ff. – MEKK1 504 – lysosome-associated membrane protein – pathway 1063 (LAMP) 603 melanoma 685, 852 – secretory 604 melanoma-associated tumor antigen (MAGE) 112, 505 m membrane M-791 873 – blebbing 572 M-826 873 – ceramide-enriched macrodomain 997 ff. M-920 873 – ceramide-enriched membrane platform M3/6 957 997 ff. macbecin 942 ff. – sphingolipid-rich domain macrophage 648 ff. 1058 – anti-inflammatory effect 655 f. – liquid-ordered and -disordered status 1002

– antitumor (M1) 657 ff. – potential (DCm) 186, 286, 352, 497, 770 – differentiation 274 MEROPS database 224 – inflammatory protein-1b 782 metastasis 687, 714, 778 – pro-inflammatory effect 655 f. methoxyestradiol 1099 – protumor (M2) 657 ff. methyl-CpG binding domain protein – tumor-associated (TAM) 647 ff. (MDP4) 809 magnetic resonance imaging, see MRI methylation 784, 1015 – aberrant 714, 972 – hallmark traits 946 – hypermethylation 853 mammalian Sterile20-like MG132 1075 –1(Mst-1) 493 MGMT, see O6-methylguanine-DNA methyl- –2(Mst-2) 504 transferase 1120 Index

microarray-based expression profiling 692, MMR, see mismatch repair 728 ff. MMP, see matrix-metalloprotease micronucleation 1051 ff. MnSOD, see manganese superoxide dismutase – micronuclei (MN) 1060 model microscopy – composite 686 – epifluorescence 711 – animal model of tumor lymphangio- – intravital 689 genesis 1102 – total internal reflection microscopy 711 modeling microspot kinetics 731 ff. – temporal and spatial complexity 686 – ideal 731 ff. molecular chaperone 933 ff. – mass flux-limited binding 732 molecular imaging 705 ff. – mixing 735 – anatomical assessment 705 ff. – reaction mechanism 733 ff. – cancer biomarker 705 MIH, see inhibitor of apoptosis proteins – cell migration and trafficking 709 milk fat globule epidermal growth factor – early diagnosis 705 ff. (EGF) factor 8 (MFG-E8) 627, 653 – invasion 706 mismatch 829 ff. – metastasis 707 ff. mismatch repair (MMR) 823 ff., 842 – molecular aberration 705 mitochondria 347, 362, 432, 573 ff., 1052 ff. – molecular footprint 705 – cell death pathway 383 – molecular profiling 705 – fission 351, 578 – monitoring tumor burden 709 – fusion 351 – mouse model 688 – import 502 – oncogenic and viral transformation 709

– membrane potential (DCm) 186, 286, – p53 714 352, 497, 770 – precancerous lesion progression 706 – mitochondrial ceramide-enriched – premalignant state 714 membrane platform 1006 – protein-protein interaction 709 – mitochondrial intermembrane space (IMS)- – real-time 705 ff. resident protein 225, 286 – signal transduction 709 – mitochondrial outer membrane – therapeutic efficacy 708 permeabilization (MOMP) 758 ff. molecular imaging modality 708 ff. – mitochondrial pathway 4, 497, 542 – anatomy based imaging 688 – mitochondrial permeability transition pore – bioluminescence 688 f., 709 f. (MPTP) 188 – charged-coupled device (CCD) 689, 710 – mitochondrial permeabilization 578 – epifluorescence microsopy 711 – mitochondrial reticulum 578 – fluorescence imaging 688 f., 709 f. – role in apoptosis 362 – in vivo optoelectronic, confocal and – serine protease 222 ff. multiphoton microscopy 711 mitogen-activated protein kinase (MAPK), – metabolic 688 see also MEK 95, 809, 915, 957 – multimodality imaging 713 – ERK 491 ff. – nuclear imaging 709 f. – MAPK kinase 7 (MKK7) 108 – optical imaging 709 f. – MAPK kinase kinase (MAPKKK/MAP3K) – photon sensing device 711 504, 767, 915 – total internal reflection microscopy 711 – MAPK phosphatase (MKP) 450 f. – ultrasound imaging 688 – p38 610, 957 molecular imaging probes 708 ff. – p44/p42 610 – antibody-antigen 709 – signaling 493, 716, 1063 ff. – injectable radiopharmaceutical mitotic apparatus 429 – distribution 708 mitotic catastrophe 799, 1060 – fluorescent protein 708 mixed lineage kinase (MLK) 494 ff. – ligand-receptor 709 Miz-1 1055 – metabolism 708 ML-IAP, see inhibitor of apoptosis proteins – nonspecific 708 MM1 542 – peptide-receptor 709 Index 1121

– pharmacokinetics 709 MSX-domain containing transcriptional – probe-target interaction 709 regulator 504 – quenching-dequenching 709 mTOR, see mammalian target of rapamycin – smart probe (molecular beacon) 690, 708 ff. mucosa-associated lymphoid tissue (MALT) – specificity 708 13, 419 – targeted 708 f. – lymphoma 917 – uptake 708 multidrug resistance 335 morphological phenotype 1051 – gene (MDR1) 898 mortalin-2 955 multiple sclerosis disease (MS) 140 mouse muristerone A 677 – conditional knockout 675 ff. mutagenesis 691 – Em-myc transgenic 677 ff. mutation 14 f., 170, 277, 365, 530, 552, 781, – “gain-of-function” 675 891 ff., 971 ff., 1018, 1040 ff. – genetically engineered 677 MutL homolog 1 (MLH1) 829 ff. – immunocompromised 673 ff. MutS homolog (MSH) 829 – knockdown 676 – MSH2 829 ff. – knockin 676 ff. – MSH3 829 ff. – knockout 675 ff. – MSH6 829 ff. – “loss-of-function” 675 MX-1013 (zVD-fmk) 873 f. – nude 673 MX-1122 873 f. – 677 Mxi2 224 – regulatable transgenic 677 myc 490 ff., 541 ff., 613, 678 f., 1021, 1055 – scid (severe combined immuno- – Bcl-2 14 deficiency) 673 ff. –c-myc 177, 393, 478, 766 ff., 898 – transgenic 675 ff., 974 – Em-myc transgenic mouse 677 ff. – treatment sensitivity of cancer 681 – lymphoma 685 mouse embryonic fibroblast (MEF) 786 – myc-induced lymphomagenesis 277 mouse mammary tumor virus (MMTV) – N-myc 14 682 – transgenic mouse 682 mouse model 671 ff., 1066 – all-in-one model 673 n – cancer 680 N-CoR (nuclear receptor corepressor) 1017 – genetic engineering 675 Na+/Ca2+-exchanger (NCX) 574 ff. – imaging 688 Na+/K+-ATPase 584 – model system in mouse 673 NAD+ 1059 – orthotopic model 674 NAIP, see inhibitor of apoptosis proteins – pathway model 673 National Cancer Institute of Canada (NCIC) – reporter system 690 1034 – transplant model 673 ff. natural born killer (NBK) 1039 – treatment model 673 natural killer (NK) cell 764 – tumor-host interaction model 673 NECA (5’-N-ethylcarboxamideadenosine) mouse mutant mnd2 202 945 MRE11 828 ff. necdin 504 MRE11, RAD50 and NBS1 (MRN) 831 ff. necrosis 3, 109, 851, 1051 ff. MRI (magnetic resonance imaging) 688, – programmed 1059 712 ff. Nedd4-like family 540 – Brownian motion of water 719 Neisseria gonorrhoeae 1003 – diffusion MRI 712 ff. NEMO 446 – noninvasive assessment 712 ff. neoangiogenesis 686 – volumetric tumor response 719 neogenin 161 ff. MS-275 N-(2-Aminophenyl)-4- nerve growth factor (NGF) 171 [N-pyridine-3-yl-methoxy-carbonyl)amino- netrin-1 receptor 159 ff. methyl]benzamide 1020 ff. neu 683, 770 mSin3a 787 neural development 169 1122 Index

neural precursor cell 1042 nucleophosmin gene (NPM) 783 neuroblastoma 853, 918 nucleotide excision repair (NER) 799 ff., neurodegenerative disease 250 823 ff., 842 neurofibroma 686 nucleotide-binding oligomerization domain – neurofibromatosis gene (NF1) 686 (NOD) 288 ff. neuronal apoptosis inhibitor protein, Nur 77 581 see inhibitor of apoptosis proteins NURD (nucleosome remodeling and neutrophil 1001 deacetylation) 1017 nevoid basal cell carcinoma syndrome nutlin 895 (NBCCS) 177 nystatin 1002 Newcastle disease virus (NDV) 66 NF-kB (nuclear factor) 44, 93 ff., 127, 419, o 445 ff., 472, 491, 503, 530, 760 ff., 782, O6-methylguanine 799 852, 901, 951 f. O6-methylguanine-DNA methyltransferase – activation 716, 952 (O6MeG, MGMT) 800 ff. – c-Rel 445 Oblimersenr 1038 – essential modifier 446 oligodendroglioma 1037 – inhibitors 456, 1075 f. Omi/HtrA2, see HtrA2/Omi – NF-kB1/p105/p50 445 oncogene 419, 691 – NF-kB2/p100/p52 445 – oncogenesis 658 – pathway 915 ff., 1063 – oncogenic fusion protein 678 – Rel homology domain (RHD) 445 – oncogenic kinase 1022 – RelA/p65 445 ONYX-015 904 – RelB 445 oocyte 1001 – transcriptional control 1065 – cell death 274 – tumorigenesis 452 OSI-774 (erlotinib, tarcevar) 1069 NGF, see nerve growth factor osteopontin (OPN) 778 Niemann-Pick disease type A 998 osteoprotegerin 33 Nijmegen breakage syndrome 840 osteosarcoma 853 nitrite oxide synthase (NOS) 581, 1064 OSU-03012 982 Nogo receptor 171 OSU-03013 982 Non-PIKK PKB regulators 469 outer mitochondrial membrane (OMM) nonsteroidal anti-inflammatory drug 286, 498 (NSAID) 456, 1073 – rupture 578 NORE1 493 ovarian cancer 918 norfloxacin 605 oxamflatin 1025 novobiocin 944 oxygen Noxa/APR 328 ff., 389 ff., 542, 786, 892, – oxygen regulated protein 150 (ORP150) 1052 ff. 790 – BH3-only protein 379, 390, 762 ff. – transport 1064 – hypoxia 389 – molecular mechanism 390 p – noxa-/- mice 391 P4 position in tetrapeptide substrates 264 – p53 379 ff. p14ARF 892 ff. – tumorigenesis 394 ff. p15ink4B 479 NRAGE/MAGE-D1/Dlxin-1 (neurotrophin p16INK4a/ARF 685 ff. receptor-interacting MAGE homolog) p21waf1/cip1 381, 473, 528 ff., 690, 787 f., 416 ff., 505 892 ff., 1016 ff., 1041, 1055 NSM, see sphingomyelinase – p21-activated kinase (PAK) 498 f. nuclear imaging 712 ff. p23 939 ff. – crosslinked iron oxide nanoparticle 718 p27kip1 473, 1021 – g-emitting radio nuclides 713 p34cdc2 429 – preclinical application 717 p35 411 – radioactive substrate 712 p38, see mitogen-activated protein kinase Index 1123 p44/p42, see mitogen-activated protein kinase – response to genotoxic stress 517 ff. p50cdc37 768, 939 ff., 951 f. – senescence 891 p53 189, 299, 331 ff., 349 ff., 379 ff., 472, – siRNA 680 f. 517 ff., 686 ff., 766 ff., 783, 825 ff., 841, – target gene 519 ff. 852, 951 ff., 1073 – therapeutic strategy 893 ff. – acetylation 893 – transactivation 788, 901 – activation 605, 782, 1055 – transcriptional activity 519 ff., 901 – antiapoptotic signaling 528 f. – translocation to mitochondria 522 – antibody 897 ff. – transrepression 788 – apoptosis 517 ff., 783, 812 f., 891 – tumor suppressor 678 ff., 781 ff., 918 – Bid 385 p55 TNF-R 32 – breast cancer 842 p60hop 939 ff. – cell cycle arrest 381, 528, 891 p70 S6K 467 – cell death signaling 382 ff. p73 472, 536 ff., 893 ff., 951 – cellular aging 891 – null mouse 538 – cellular stress 891 – proapoptotic mechanism 542 – chemotherapy 906 p75NTR/low-affinity neutrophin receptor – cytosolic 523 ff. 158 ff., 505 – death receptor signaling 383 p100 446 – DNA binding 897 ff., 1024 p105 446 – DSB repair and surveillance 839 p150Glued 273 – gain-of-function 898 p300/cAMP-responsive element-binding – gene alteration 1062 protein (CBP) 539, 788, 1017 – 903 paclitaxel 608, 682, 895 – genomic stability 838, 891 Par 503 – heat shock 891 PARP, see poly-ADP ribose polymerase – hematopoietic stem cell 680 paraptosis 851 – hypoxia 785 f., 891 Parkinsonism 250 – imaging 714 f. patched (Ptc) 163 ff. – influence of Mdm2 474, 526 pathogen-associated molecular pattern – knockout 678 ff., 1077 (PAMP) 651 – mitochondrial 522 ff. pattern recognition receptor (PRR) 651 ff. – mitochondrial cell death pathway 383 Pctr1 691 – mutant 15, 530, 781, 891 ff., 1042 PED/PEA-15, see phosphoprotein enriched – nontranscriptional activity 522 ff. in diabetes/phosphoprotein enriched in – oncogene activation 891 astrocytes 15 kDa – ovarian cancer 842 pentraxin 653 – p53-/- mouse 64, 380, 392 perifosiner (D-21266, octadecyl-(N,N)-dimethyl- – p53+/- mouse 678 piperidinio-4-yl)-phosphate) 983, 1069 – p53/mdm2 binding 895 ff. permeability transition 579 – p53AIP1 (p53-regulated apoptosis – pore (PTP) 4, 286, 347, 574 ff. inducing protein 1) 539 peroxisome proliferator-activated receptor g – p53-responsive gene 3 (PRG3/AMID) ligand 854 207, 237 peroxynitrite (ONOO-) 581 – p53 reactivation and initiation of massive PERP 542, 786 ff. apoptosis, see PRIMA-1 PERK, see eukaryotic translation initiation – pathway 904, 1034 ff. factor (eIF) – phosphorylation 893 PET (positron emission tomography) 688, – post-translational modification 893 709 ff., 778 – proapoptotic signaling 518 ff., 659 PETCM 303 – proteasome 1075 phagocyte 648 ff. – reactivation of the p53 apoptosis pathway – paradigm for polarized M2 mononuclear 891 ff. phagocytes 659 – regulation 380 – receptor 626 ff. 1124 Index

phagocytosis 3, 586 f. phosphorylcholine 609 – postphagocytic response 636 photooxidation 614 phagosome 648 pleckstrin homology (PH) domain 1056 PH, see pleckstrin homology PI3K, see phosphoinositide 3-kinase PH domain leucine-rich repeat protein PI3K/Akt/mTOR pathway 966 ff., 1056 ff. phosphatase (PHLPP) 466 – cancer prevention 974 PHAP1 303 – inhibition 976 phenotype – tumorigenesis 974 – phenotype-to-gene screen 692 PIA, see phosphatidylinositol ether lipid – phenotype-to-genotype strategy 680 analog – tolerant 802 PIDD (p53-induced protein with a DD) 814 phosphatase and tensin homolog deleted PIDDosome 814 on 10 (PTEN) 462, 481, Pim family 953 950, 968 ff. Pin1 541 – deletion 971, 1040 Pivanex 1026 – loss 971 PKC, see protein kinase C – mutation 971, 1040 plasma membrane Ca2+-ATPase (PMCA) 573 ff. – PI3K 1056 ff. platelet-activating factor receptor 1003 – promoter methylation 972 platelet-derived growth factor (PDGF) 463, – reconstitution 977 1039 phosphatidylinositol ether lipid analog platelet-endothelial cell adhesion molecule-1 (PIA) 984 (PECAM-1), see CD31 – PIA5 978 point mutation 1018 – PIA6 978 poly-ADP ribose polymerase (PARP) 110, – PIA23 978 242, 271, 825, 1059 – PIA24 978 –PARP-1 1059 – PIA25 978 post-translational modification 1015 D-3-deoxy-phosphatidyl-myoinositol ether PP2A, see protein phosphatase 2A lipid (PX-316) 984 PPM1D 893 phosphatidylinositol-(4,5)-bisphosphate PRIMA-1 (p53 reactivation and initiation

(PIP2) 1056 of massive apoptosis) 901 ff., 1036 phosphatidylinositol-(3,4,5)-trisphosphate – PRIMA-1MET 906

(PI(3,4,5)P3, PIP3) 463, 1056 proangiogenic factor 1091 phosphatidylserine (PS) 586 f. programmed cell death (PCD) 600 – receptor 586 – apoptosis-like 1052 phosphoinositide 3-kinase (PI3K) 462 ff., – caspase-independent 608 ff. 473 ff., 491 ff., 611 ff., 764, 949 ff., 966 ff., – lysosomal 604 1057 – necrosis 1052 – activation 967 ff. proliferating cell nuclear antigen (PCNA) – inhibitor 977 ff. 825 ff. – PI3K-related kinases (PIKKs) 466 prolyl hydroxylase (PHD) 770 3l-phosphoinositide-dependent kinase (PDK) promoter – inhibitor 981 – cell-type specific 679 – PDK-1 463, 949 ff., 982, 1056 – interferon (IFN) inducible promoter 677 – PDK-2 950 – methylation 784, 972 phospholipase promyelocytic leukemia protein (PML) 540

–A2 (PLA2) 582, 769, 1057, 1072 f. prostate cancer 588 –C(PLC) 1073 proteasome 940 ff. phospholipid 1068 – inhibitors 854, 1025, 1078 f. – synthetic analog 1068 ff. – proteosomal degradation 328 phosphoprotein enriched in diabetes/ – subunit 272 phosphoprotein enriched in astrocytes 15 protein folding 933 ff. kDa (PED/PEA-15) 226, 1042 protein inhibitor of activated STAT-1 phosphorylation 328 (PIAS-1) 539 Index 1125 protein kinase A 499 – p53-independent regulation 387 protein kinase B (PKB/Akt) 462 ff., 475 ff., –Puma-/- mice 391 491 ff., 685, 764 ff., 949 ff., 966 ff., 1056 ff. – tumorigenesis 394 ff. – activation 968 ff. PX-316, see D-3-deoxy-phosphatidyl- – AGC kinase subfamily 464 myoinositol ether lipid – Akt binding protein 968 PXD-101 1020 ff. – Akt signaling inhibitor-2 (API-2) 985 pyrimidine dimer 805 – Akt-in 986 pyroxamide 1025 – amplification 973 pyruvate kinase 1064 – API-59CJ-OMe 985 – apoptosis 470 q – carcinogen 975 Q-VD-OPH (quinolyl-Val-Asp(OMe)-[2,6- – clinical specimen 970 difluorophenoxy]-methyl-ketone) 873 – consensus sequence 969 – inhibitor 983 ff. r – isoforms (Akt1, Akt2, Akt3) 968 Rab protein family 604 ff. – isoform-specific inhibitor – Rab25 604 ff. (Akti1, Akti2, Akti1,2) 985 – Rab27a 604 ff. – phosphorylation 968 RAD001 987 – PI3K/Akt/mTOR pathway 966 ff., 1037 ff. RAD51 831 ff. – PIK3CA 972 RAD52 831 ff. – prognosis in cancer 970 radiation 758 – regulation 968 – apoptosis 1051 ff. – substrate 470 ff., 969 – dose 1050, 1078 – transgenic mouse 974 – induced side effect 1076 protein kinase C (PKC) 765, 1057, 1071 – intensity-modulated radiation therapy – inhibitor 1071 ff. (IMRT) 1050 – PKC-412 1071 ff. – resistance 1049 ff., 1060 ff. protein microarray 729 ff. – response pathway 1049 – antibody microarray format 740 – sensitivity 1049, 1060 ff. – cancer diagnosis 744 – therapy 778, 892 ff., 1025, 1034, 1049 ff., 1070 f. – data analysis 742 – tissue damage 1049 – experimental design 741 radicicol 942 f., 954 – kinetics 731 ff. radiobiology 1050 – sample collection 741 – targeted modulation 1050 protein phosphatase Raf kinase 490 ff., 502 ff. – ceramide-activated 1057 – c-Raf 1057 protein phosphatase 2A (PP2A) 765, 951 raft 1058 Protein S 627 RAIDD (receptor-interacting protein proteolysis 270 (RIP)-associated ICH-1 homologous – cleavage 328 protein with a DD) 99, 814 – processing 93 rapamycin 685, 986 protooncogene 552 Raptor 468 PS-341 (bortezomib) 1075 ras oncogene 490 ff., 612 f., 679, 770 Pseudomonas aeruginosa 1003 – binding domain (RBD) 494 PTEN, see phosphatase and tensin homolog – cascade 1063 deleted on chromosome 10 – H-ras oncogene 677 PU24FCL 944 – kinase suppressor of ras (KSR) 494, 1057 PU3 944 – subfamily 492 Puma/Bbc3 277, 328 ff., 385 ff., 786, 892 – transgenic mouse 682 – BH3-only protein 379, 388, 762 ff., 1052 ff. rational design 319, 338 –ERstress 387 RB (retinoblastoma) 551 ff., 672 ff., 689, 1024 – molecular mechanism 388 – phosphorylation 556 – p53 379 ff. – terminal differentiation 557 1126 Index

reactive nitrogen intermediate (RNI) 659 s reactive oxygen intermediate (ROI) 659 SAHA (suberoylanilide hydroxamic acid) 1016 ff. reactive oxygen species (ROS) 108, 580, SAHB (stabilized a-helix of Bcl-2 domains) 606, 769 f., 1024, 1064 1038 Reaper 414 SAM domain 537 Reaper, Hid, Grim (RHG proteins) 296, 921 saquinavir 1075 rearranged during (RET) 162 ff. SC-236 1074 receptor clustering 1058 scavenger receptor 586, 653 receptor interacting protein-1 (RIP-1) 38, 610 Schwann cell 686 receptor tyrosine kinase (RTK) 162, 462, Scotin 542 627 f. scramblase 586 recombinase 676 ff. second mitochondria-derived activator of recombination 823 ff., 841 f. caspase/direct IAP-binding protein with –Cre-mediated 677 ff. low pI (Smac/DIABLO) 42, 104, 197, – homologous (HR) 675, 822 ff. 223 ff., 406, 432, 685, 759 ff., 850, 865 ff., – meiotic 837 914 ff., 948 ff., 1036 ff., 1059 – mitotic 837 – apoptosis 4 f., 785 – surveillance 838 – mimetic drug 881 f. renal cell carcinoma 419 – peptide 855, 881 f., 1036 reoxygenation 787 – Smacb 882 replication secretory leukocyte protease inhibitor – fork 822 ff., 839 ff. (SLP1) 655 – replication protein A (RPA) 827 ff. serine protease 582 repulsive guidance molecule (RGM) 161 ff. – inhibitor 2A (Spi2A) 611 resistance 849, 892, 1057 serum amyloid P 653 respiratory chain 247 serum and glucocorticoid-induced protein resveratrol 456 kinase (SGK) 1056 retinoic acid 1025 SHC 493 retrovirus Sickle 414 – avian 1039 sigma-2 receptor 605 ff. – retroviral insertional mutagenesis 691 signaling – retroviral transduction 676 ff. – ceramide 997 ff. RHG protein 296, 921 – clustering 1005 rhinovirus 1003 – PI3K/Akt/mTOR pathway 966 ff., 1056 ff. Rictor 468 sindbis virus 1003 RING (really interesting new gene) Sir2 family 1016 – motif 418, 917 Sir3 1017 – zinc finger (RZF) 42, 405, 916 siRNA, see RNA interference 337 RITA (reaction of p53 and induction of sister chromatid exchange (SCE) 838 f. apoptosis) 896, 1036 Smad 479 f., 918 rituximab 1000 small cell lung carcinoma (SCLC) 765 RNA sonic hedgehog (shh) 157 ff. – m7G-cap structure 412 SOS 493 – gene-specific siRNA knockdown SP12 111 technology 685 SPECT (single photon emission computed – interference (RNAi) 337, 430, 676, 692, tomography) 688, 709 ff. 855 spectral karyotyping (SKY) 692 – retroviral siRNA libraries 692 sphingolipid 1002 – siRNA 337, 893, 1024, 1038 – sphingolipid-rich cell membrane domain ROCKI 273 1058 roscivitine 856, 896 sphingomyelin 609, 997, 1054 RTP801/REDD1 782 sphingomyelinase (SMase) 1054 f. Rubinstein-Taybi syndrome 1018 – acid (ASM) 606, 997, 1053 ff., 1077 Runx transcription factors 472 – ASM deficiency 1057 Index 1127

– ASM knockout 1057, 1077 temozolomide 1034 – factor associated with neutral SMase teniposide 760 (FAN) 609 tetracyclin-regulatable system (Tet system) 677 – neutral (NSM) 1055 thalidomide 1100 sphingosine 605 ff. thapsigargin 585 ff. Spike 576 therapy spinocerebellar ataxia type 1 (SCA1) 481 – cancer 44 ff., 228, 282 ff., 299 ff., 318, spleen tyrosine kinase (Syk) 610 335 ff., 639, 891 ff., 997 ff. src – combined treatment 1080 – SRC-1 1017 – therapeutic approaches 892 ff. –v-src 770 – therapeutic gain 1076 Staphylococcus aureus 1003 – resistance 892 STAT (signal transducer and activator of thioredoxin (Trx) 108 transcription) 272, 491, 1022 f., 1063 –Trx-binding protein (TBP2) 1024 staurosporine 605 ff., 982, 1071 thymidine kinase 708 steroid hormone 946 thymidylate synthase 1022 ff. – receptor 938 ff. TIAP, see inhibitor of apoptosis proteins STI571 (Gleevecr, Imatinib) 1039 f. tirapazamine 778 stress 757 ff., 891 ff. tissue – genotoxic 799 – homeostasis 3, 551 f. stress-activated protein kinase (SAPK) 538, – invasion 714 760 ff., 957 – normal tissue damage 1049, 1077 – SAPK kinase (SEK) 766 ff. TNF, see tumor necrosis factor structural imaging 712 TNF family 6, 759 structure-activity relationships (SARs) 922 – natural ligand for death receptor 6 sulindac 200 TNF homology domain (THD) 93 SUMO ligase 539 TNF receptor 605, 759 ff., 948, 998 super paramagnetic iron oxide 712 – TNF-R1 93 surfactant protein – TNF-R2 93 –A 653 TNF/NGF superfamily 5 – C1q 653 TNF-R-associated factor (TRAF) 96 ff., 418, –D 653 504, 915 survival pathway 1063 ff. – TRAF2 depletion 106 survivin/TIAP/BIRC5 13, 419, 428, 854, TNF-R-associated DD protein (TRADD) 878, 915 ff., 954 99 ff., 760 – BIR domain 924 TNF-related apoptosis-inducing ligand – IAP family 787, 917, 1036 ff. (TRAIL)/APO2L 32, 48, 685, 759, 850, – phosphorylation 434 865 ff., 1025, 1036 ff., 1063 ff. – profiling 433 –AdTRAIL 53 surviving fraction 1061 – allogeneic hematopoietic stem cell transplantation 70 t – antibody 1067 T cell 61 f., 673 – apoptosis 40, 1064, 1078 – lymphoma 1025 ff. – Bcl-2 1066 TAB1 915 – cancer therapy 44 ff. TAFII p250 1017 – DISC 36 ff. TAK1 MAPKKK 915 – immune surveillance 62 TAM, see tumor-associated macrophage – in vitro 1066 tamoxifen 677 – mouse model 1066 tarcevar (OSI-774, erlotinib) 1069 – physiological role 61 Taxol 287 – radiation therapy 1066 f. TCL1 469 – TRAIL-/- mouse 63 TEAD/TEF 472 – toxicity 923 technetium 718 – ubiquitin/proteasome system 43 1128 Index

– viral infection 65 trichothiodystrophy (TTD) 827 f. TNF-related apoptosis-inducing ligand TSA 1025 receptor (TRAIL-R) 31 ff., 45 ff., 142, TsIAP, see inhibitor of apoptosis proteins 383, 926 tuberin 467 – monoclonal antibody 50 a-tubulin 1023 – TRAIL-R1/DR4 32 ff., 45 ff., 69, 95 ff., tumor 851, 1037 – apoptosis-resistant 1062 – TRAIL-R2/DR5/APO-2/Killer/TRICK2 – cell inactivation 1061 32 ff., 45 ff., 69, 95 ff., 851, 1037 – cell line 671 – TRAIL-R3/DcR1/TRID/LIT 33 ff., 45, 853 – counterattack 16 – TRAIL-R4/DcR2/TRUNDD 33 ff., 45 – development 561 TNF/TNF-R superfamily 32, 850 – hemangiogenesis 1089 Toll-like receptor (TLR) 650, 864 – immunosurveillance 674 ff. topoisomerase I (Topo I) 823, 841 f. – interference with DR-mediated TRAIL, see TNF-related apoptosis-inducing apoptosis 13 ligand – lymphangiogenesis 1090 ff. TRAIL-induced signaling 36 – microenvironment 649, 671 TRAIL-TRAIL-R system/TRAIL Receptor- – pathogenesis 647 Ligand system 31 ff. – resistance mechanism 13 ff. TRAMP/DR3 32 – suppression 318, 674 transcription factor 1022 – suppressor 171, 334, 552 f., 691, 1035 – basic helix-loop-helix (bHLH)-PAS – survivin 13 transcription factor family 781 – tumorigenesis 536 ff., 672 – CCAAT-binding transcription factor tumor necrosis factor (TNF) 93 ff., 504, (CTF) 541 609 ff., 659, 952 – E2F transcription factor 539, 552 f., – TNF-a 759 ff., 851, 865 ff., 953 787, 1022 – transmembrane TNF (memTNF) 94 ff. –Forkhead box class O transcription factors – soluble TNF (sTNF) 94 ff. (FOXO) 471 ff., 950 f., 1063 tumor-associated macrophage (TAM) 647 ff. – HSF-1 (heat shock transcription factor-1) TUNEL 779 936 TWEAK-R 106 – Runx transcription factors 472 tyrosine kinase-like (TKL) kinase 494 – transcription factor II H (TFIIH) 827 transcriptional regulation 503, 556 u transcriptome-based comparative analysis 692 ubiquitin 940 transformation 3, 462, 613 – polyubiquitin 940 transforming growth factor (TGF)-b 654 ff. ubiquitin/proteasome system 43, 826, 940 ff. – signaling 479 ubiquitination 328, 781, 901, 916, 942, 1015 – TGF-b receptors 479, 494 UCN-01 982, 1071 ultrasound imaging 688 – regulatable 679 UNC5H 161 ff. transglutaminase 582 unfolding protein response (UPR) pathway translesion synthesis (TLS) 841 575, 768, 789 f. translocase of inner mitochondrial UV 823 ff., 998 ff. membrane (TIMM13b) 209 – crosslink 828 translocation 691, 831 ff., 917, 1018 – lesion 842 transmembrane potential (DCm) 186, 286, – radiation 760 352, 497 – skin cancer 842 transporter –UV-C induced apoptosis 805 – uniport 573 ff. treatment v – combined 1080 vaccina virus 111 tricarboxylic acid (TCA) cycle 770 vacuolar-type proton ATPase (V-ATPase) 602 trichostatin A 787, 1018 valproic acid 1026 Index 1129 vascular endothelial growth factor (VEGF) wip1 893 657 f., 686 ff., 777, 898, 1092 ff. Wnt pathway 477 – receptor 1073 wortmannin 977 ff. vasculogenesis 1088 WW domain-containing oxidoreductase V(D)J recombination 831 ff. (WOX1) 210 viral FLICE-inhibitory protein (v-FLIP) 121 WX514 945 virus 998 – adenovirus 852, 903 f., 1035 x – avian retrovirus 1039 XAF1 (XIAP-associated factor 1) 416, 854, – HIV 67 883, 917 – Hodgkin’s lymphoma 917 X-box-binding protein-1 (XBP-1) 790 – human papilloma virus (HPV) 893 X-chromosome-linked IAP (XIAP) 42, 108, – mouse mammary tumor virus (MMTV) 199, 223 ff., 297, 409 ff., 431, 505, 759, 854, 682 878 ff., 914 ff., 925 f., 1036 ff. – Newcastle disease virus (NDV) 66 – antagonists 882 – non-Hodkin’s lymphoma 918 – antisense targeting 878 ff. – retrovirus 676 ff., 691, 1039 – mechanism of caspase inhibition 881 ff. – rhinovirus 1003 X-ray computed tomography (CT) 688 – sindbis virus 1003 xenograft model 852 – vaccina virus 111 xeroderma pigmentosum (XP) 827 f., 841 f. voltage-dependent anion channel (VDAC) 241, 286, 352, 500, 578 f. y von Hippel-Lindau (VHL) 770, 781 f. YES-associated protein (YAP) 472, 541 VX-740 (Pralnacasan) 874 VX-765 874 z VX-799 874 ZD1839 (gefitinib, Iressar) 1040, 1069 zVAD-fmk (benzyloxycarbonyl-Val-Ala-Asp- w fluoromethylketone) 277, 604, 871, 1024 Walkerls box 291 zVD-fmk (MX-1013) 873 f. WD-40 repeat 288 ff. zymogen 4,168, 262 ff., 913 Wee1 kinase family 475 Werner’s syndrome (WS) 687 – protein (WRN) 838 ff.