Index
367 A
A20, 95, 98, 101–102 A20⫺/⫺, 101
A20-deficient mice, 101 ABIN-1, 102
ABIN-2, 102 Acetylation, 203
Acid sphingomyelinase, 99, 325 Acinus, 13
Actinomycin D, 117, 194 Activation of caspase-10, 124 Activation of p53, 201
Activation of procaspase-8, 120, 122 Active caspase-8, 120
Adaptor, 6–7, 93, 102, 123 Aggregation of CD95, 120 AICD, 50
AIDS, 28, 134, 149 AIF, 12, 19
Akt, 27–28, 43, 47–49, 51, 55, 98, 138, 165, 263, 313
Akt inhibitors, 55 ALPS, 28, 124, 152
Alternatively spliced genes, 327 Androgen independence, 52 Angiogenic switch, 45 Annexin V, 56
Anoikis, 48
Antiangiogenic agents, 54 Anti-angiogenesis, 204 Antibacterial defenses, 4
Apaf-1, 2–4, 6–8, 15, 17, 19, 29, 52, 95, 116, 120, 122, 135, 149, 204, 208, 212 Apaf-1⫺/⫺, 18
Apaf-1⫺/⫺ knockout mice, 219 APO1L, 20, 22
APO2L, 20, 22, 133, 233 Apo3, 232
APO-3/TRAMP, 116 Apoptosis, 204
Apoptosis effector, 113 Apoptosis initiator, 113
Apoptosome, 6, 8, 15, 17, 21, 27, 211 APRIL, 71, 73
ASK1, 90, 95, 97–98, 100, 236 ATM, 28, 202
ATP, 8, 19 ATR, 28, 202 ATRA, 189, 249 5-Aza-C, 217 B
Baculovirus, 11
Bad, 15, 27, 47, 138, 220 BAFF, 66, 71–73 BAI1, 204
Bak, 3, 14, 16, 26, 139, 212, 233 Bax, 3, 14, 16, 26–28, 45, 204, 233 Bax-deficient cells, 139
B-cell lymphoma, 52
Bcl-2, 3, 14–16, 21, 29, 44–45, 52, 102, 112, 119, 135, 139, 150, 213, 312
Bcl-2⫺/⫺, 16 BC loop, 70
Bcl-XL, 3, 21, 26, 29, 45, 102, 139, 233 BCMA, 281
BH3-only protein, 12, 15-17, 28, 46–47, 55, 112
BH3 domain, 16
Bid, 3, 12-13, 15, 17, 21, 26–28, 94-96, 112, 115, 119, 135–137, 211–213, 221, 233 Bid⫺/⫺, 26
Bid-deficient thymocytes, 96 Bid phosphorylation, 239
tBid, 15, 17, 21, 26, 135, 137, 139, 220, 233 Bik, 15, 46
Bim, 3, 27–28 Bim⫺/⫺, 18 Bim knockout, 16 BIR1, 9–10 BIR2, 9–10 BIR3, 9–10 BIR domain, 9
Bladder transitional cell carcinoma, 154 Blk, 15
Bmf, 15 Bok, 14
Bortezomib, 49, 51 Bruce, 9, 328
Bystander effect, 140, 330 C
CAD, 12, 19, 112, 137 Calcineurin, 165 Camptothecin, 49 Cancer, 150, 222
Cancer therapy, 222, 263, 356, 358, 361 CAPP, 327
CAP proteins, 24 CAR, 342 CAR1, 232
CARD, 6–7, 9–10, 26, 113–114, 210, 213 CASH, 117
CASP8 methylation, 215–216 Caspases, 5, 11, 111
Caspase-1, 6, 112–113, 120, 209
Caspase-2, 3–4, 6–7, 13, 17, 95, 97, 112–
113, 115–116, 120, 209
Caspase-3, 6–7, 9–13, 21, 26–27, 95, 101, 112–113, 115, 135–136, 139, 209 Caspase-4, 112–113
Caspase-5, 112–113, 209
Caspase-6, 6–7, 12–13, 21, 26–28, 112–
113, 115, 209
Caspase-7, 6–7, 9–13, 17, 21, 26–27, 101, 112–113, 115, 135–136, 139, 209 Caspase-8, 3–4, 6–9, 11–13, 21, 24–26, 51,
95–96, 99, 102, 112–113, 115–121, 124, 135–137, 139, 149, 208–211 Caspase-8 activation, 126
Caspase-8-deficient T-cells, 96 Caspase-8⫺/⫺ mice, 214, 249
Caspase-9, 3–4, 6–13, 15, 17, 21, 26–27, 95, 112–113, 115–116, 120, 136, 139, 209, 218
Caspase-9⫺/⫺, 18 Caspase-9⫺/⫺ mice, 218
Caspase-10, 3–4, 6–8, 13, 21, 25, 29, 112–
113, 115–118, 120, 124, 149, 208–209 Caspase-11, 112–113, 120, 209
Caspase-12, 112–113, 209 Caspase-13, 209
Caspase-14, 209
Caspase-activating complex, 116 Caspase cascade, 114
Caspase dimerization, 9 Caspase Inhibitor, 4
Caspase inhibitory proteins, 9 Caspase processing, 114 Caspase specificity, 9 Caspase structure, 114, 210 Caspase substrates, 12, 112 Casper, 117
CD27L, 71
CD28 co-stimulatory receptor, 126 CD40L, 66, 70
CD95, 23, 50, 94, 116–118, 124, 126, 164–
166 CD95 DISC, 119
CD95 in T-cell activation, 165 CD95 in viral infection, 165 CD95L, 20, 22, 126
CD95 ligand, 116 CD95 promoter, 164 CD120a, 163
CD271, 191
CD437, 191, 194–196 CD2325, 191
CEA promoter, 342 Ced-3, 2–3, 5, 14, 111, 120 Ced-4, 2–3, 111, 120 Ced-9, 2–3, 14, 111, 120
C. elegans, 1–3, 5, 14, 16–17, 19, 111, 120 Cell shrinkage, 13
Cell survival, 95, 97–98, 220 Cellular stress, 4
Ceramidase, 323, 325 Ceramide, 95, 101, 323, 325 Chemoprevention, 196 Chemotaxis, 220 Chemotherapy, 167 Chk1, 202
Chk2, 202 CLARP, 117
Clouston syndrome, 83 Combination therapy, 272 Core G-structure, 68 COX-2, 168
CpG dinucleotide, 164 CRD structure, 74 Crk11, 14
CrmA, 11, 24, 102, 324 Crohn’s disease, 164
Crystal structure of Apo2L/TRAIL, 69 C strand, 70
CTL, 176
Cutaneous T-cell lymphoma, 154 Cyclin-dependent kinases, 45 Cycloheximide, 117
Cysteine rich domains, 23, 66 Cysteine-rich repeats, 116
Cytochrome c, 6, 8, 15, 46, 52, 120, 135–
136, 149, 212 Cytokine activation, 113 Cytokinesis, 44
Cytosolic complex, 119 D
DAP-3, 102 DAP3, 135–136 Dark, 3–5 DAXX, 95, 97 DDB2, 204
Death domain, 8, 23 Death Ligand, 4, 20
DcR1, 22–23, 29, 102, 133–134, 137, 168–
169, 176
DcR2, 22–23, 29, 102, 133–134, 137, 168–
169, 176 DcR3, 22–23
DD, 8, 94, 97, 103, 114, 176, 213 Death receptor mutations, 149 Decoys, 23, 50
DED, 6–8, 11, 24–25, 94, 113–114, 117–
118, 210, 238 DED-caspase, 7 DE loops, 72–73, 75 dFADD, 4–5 DFF40, 112 DFF45, 112, 137 DIAP1, 4–5 DIAP2, 4
DISC, 2, 7–8, 20–21, 24–25, 51, 65, 94, 115, 117–119, 121–123, 125, 135, 213, 306, 324
DNA damage, 8, 45 DNA fragmentation, 12 DNA-PK, 12–13
DNA repair, 204 DNase II, 12 DOCK180, 14
Doxorubicin, 141, 202
DR3, 65, 74, 94, 102, 116, 166, 209, 213, 232 DR4, 22–23, 65, 94, 102, 116–117, 133–
137, 166, 176, 209, 213
DR4 promoter, 166
DR5, 22, 46, 50, 55, 65, 75, 94, 102, 116–
117, 133–138, 166–167, 176, 179, 191, 209, 213, 232
DR5 and p53, 167 DR5 promoter, 46, 167
DR6, 23, 65, 94, 102–103, 116–117, 168, 209, 213
DREDD, 4–5 Dronc, 3–5
Drosophila, 3–5, 11, 16, 111 Dual function of FLIP, 126 Dual regulation, 124 E
E1A, 47, 203 E1B, 47, 203 E2F-1, 44 E3, 10–11
E3 ligase, 101, 328 ECD of DR5, 68 ECM, 220
Ectodermal dysplasia, 83 Ectodysplasin, 84 ED, 83
EDA, 71–72, 84 EDA-A1, 85
EDAR, 65, 74–75, 84–87, 102–103, 265 EDARADD, 86–87, 103
Effector caspase, 115 EF loops, 68, 71 EGF, 341 EGFR, 47–48, 55 EGFR antagonists, 54 Egl-1, 3, 14
Eiger, 4 Elmo-1, 14 EndoG, 12, 19
Endosomal pathway, 118 Engulfment, 14
ErbB family, 48 ERK, 221
Executioner caspase, 6, 9
Extrinsic pathway, 13, 19, 21, 30, 149, 231 F
FADD, 2–4, 7–8, 20–21, 24, 29, 85, 94–96, 102–103, 117–120, 126, 135–136, 138, 149, 209, 212–213, 340 FADD⫺/⫺, 249
FADD-deficient cell line, 138 FADD-deficient embryos, 96 FADD-deficient T cells, 96 FADD knockout mouse, 138 FAN, 95, 98, 101
FAN-deficient mice, 101 FAP-1, 103
Fas, 20, 22–23, 27–29, 51, 55, 74–75, 95, 102, 134, 149, 212, 325
Fas/Apo1, 23, 116, 204, 213
FasL, 20, 22, 27, 29, 94–95, 133–134, 212, 325, 340
Fas Ligand ⫺/⫺, 46 Fas mutation, 153–155 bFGF, 45
FG loop, 71 FKHR, 27–28, 138 FLAME, 117 FLASH, 25, 94 Flavopiridol, 51
FLICE, 11, 24, 94, 117, 211 FLICE2, 25
FLIP, 11, 25–26, 29, 51, 94–96, 117–119, 121, 124–126, 138, 151, 233, 238, 263, 271, 306, 328
FLIP antibodies, 310 FLIP/Caspase-8 ratios, 309 FLIP-deficient mice, 96 F-Fodrin, 12–13 Forkhead, 28, 47, 138 G
GADD45, 204 GAS, 164
Gelsolin, 12–13, 115 Gemcitabine, 49 Gene therapy, 339
Genotoxic stress response, 288 Germline mutation, 152 Gld, 152, 249
Glioma, 138 GPI-linked, 134 Grb2, 95, 98 Grim, 4–5
Growth arrest, 204 Growth factor, 8, 233 GSK3G, 98
GVHD, 23 GVT, 23
H
HDAC1, 203
Hepatocytes, 140, 346 Her-2, 47–48, 55 Herpes virus 7, 168 Heterotrimers, 73 Hid, 4–5
HIF1F, 55
Histone deacetylase inhibitors, 51 Hodgkin’s lymphoma, 154
Homotrimeric structure of TRAIL, 133 Horvitz, 2
Hsp70, 19
HtrA2/Omi, 5, 19
Huntington’s disease, 114 HVEM, 281
Hypoglycemia, 45 Hypoxia, 45, 54 I
c-IAP1, 3, 9–11, 26, 95, 98, 101, 139, 233, 328
c-IAP2, 3, 9–11, 26, 95, 98, 101, 139, 233, 328
IAP binding proteins, 15 IAP cleavage, 11
IAP homologue, 101
IAPs, 2, 5, 9–11, 15, 26, 30, 52, 141, 221, 311, 328
ICAD, 12–13, 112, 115, 137 ICAD cleavage, 18
ICE, 5–6, 111, 209 I-FLICE, 117
IFN-L, 22–23, 166–167, 177 IFN receptors, 233
IGF-1, 138 Ikaros, 164 IPB F, 49, 100 IPB kinase, 49, 87, 97 IKK, 49, 87, 97, 103, 233 IKKF, 95, 97, 100 IKKG, 95, 97, 100–101 IKKG⫺/⫺, 100, 242 IKKL, 97
IKKL⫺/⫺, 242 IKK inhibitor, 49 IL-1G, 5, 111 IL-4, 164 IL-8, 45, 49
IL-10, 164 IL-12, 166 ILA, 281 ILP-1, 9 ILP-2, 4, 9
Immune privilege, 248 Inflammation, 95
Inflammatory response, 116 Inhibitor targeting, 314 Initiator caspase, 6, 115 Integrin complex, 221 Integrins, 220
Interdimer cleavage mechanism, 123 Interferon, 51, 135, 231
Interleukin 1, 101 Internalization, 164 Intracellular complex, 119
Intrinsic pathway, 13, 16–17, 26, 149 IRF1, 233
ISGF3, 244 J
JAK, 166, 233
JNK, 95, 98, 100, 103, 165, 176, 236, 323 JNK1, 328
JNK activation, 5, 85, 99, 103 K
Keratins, 12–13 Kerr, 1
KILLER, 134, 232
KILLER/DR5, 22–23, 26–28, 204–205, 290 Knob, 341
Knockout mice, 7, 12, 94 L
Lamin, 13, 115 LARD, 232
Large subunit, 120 Lck, 165
Ligand clustering, 72 Ligand mutagenesis, 77 Ligand-receptor specificity, 76 LIGHT, 71
LIT, 134
Liver damage, 134 Liver injury, 168 Livin, 9–10 Lockshin, 1
Lpr, 152, 249 LPS, 101, 164
LTF-TNFR1 complex, 67 Lymphoma, 153
Lymphotoxin, 232 Lyn, 165
M
MACH, 24, 117 MACH1, 211 Macrophages, 14 MADD, 95, 98 MALT, 153 MAP3K, 98, 100 MAPK, 95, 98
MAP kinase, 126, 165, 324 MAPKKK, 236
Maspin, 204
Mature caspase 8, 120 Mch4/FLICE-2, 117 Mch5, 211
Mdm2, 27–28, 45, 202 MEKK, 221
MEKK1, 95, 177 MEKK3, 95, 97 MEKK3⫺/⫺, 100
Melanoma, 52, 175, 178, 208 Membrane blebbing, 13 Metal-binding sites, 68 Metalloproteases, 133 Metastasis, 48
Methylation, 29, 207, 209, 214 Methylation-specific PCR, 215 Mitochondria, 8, 16, 95, 115, 135–137,
141, 149, 211 MKK4, 177, 236 ML-IAP, 10 Modulation, 271 MORT, 117 MORT1, 24 MRIT, 117 mTOR, 47, 55
MUC1 promoter, 342
Multiple myeloma, 141, 154, 281, 289 Multireceptor complexes, 77
Mutation of death receptors, 152 Mutation of Fas, 152, 154
Mutations of TRAIL-R1, 157 Mutations of TRAIL-R2, 157
Mutation of TRAIL receptor genes, 156 MX335, 191
Myc, 45, 207 MYCN, 214 N
NAIP, 328
NEMO/IKKL, 88–89, 95, 97, 101 NEMO⫺/⫺, 100
Neuroblastoma, 208 Neurotrophins, 65
NFPB, 26, 43, 47–49, 55, 85, 87, 95, 97–
103, 117, 119, 126, 134, 138, 164–
165, 167, 169, 176, 193, 195, 221, 231, 233, 241, 263, 298, 313 NGF, 65
NGFR, 102–103, 116 NIK, 95, 100, 103
NK, 22, 134, 140, 154, 176, 231, 325 Nomenclature, 283
Noxa, 15, 27–28, 46, 204 N-Smase, 101
Nur77, 196 O
ODC, 196
Oligomerization, 121 Omi/HtrA2, 4–5, 10–11
OPG, 22–23, 102, 133–134, 176, 265, 281, 289
OPGL, 265, 289 Osteoprotegrin, 134 OX40L, 66, 71 P
14-3-3 proteins, 28
p10, 5–6, 8, 113–114, 121, 232 p11, 212
p14ARF, 203 p16, 45, 212 p18, 213
p19ARF, 45, 203 p19ARF-null cells, 203 p20, 5–6, 8, 113–114, 121, 232 p21, 45
p21/WAF-1, 45, 204 p35, 11, 102
p38MAPK, 98
p53, 27–28, 43, 45–46, 51, 141, 165, 191, 195, 201, 220, 233, 290
p53AIP1, 204
p53-mediated apoptosis, 26 p53R2, 204
p53-responsive element, 165 p55, 163
p60TRAK, 98 p65, 97 p75, 65, 103 p300, 203 PAF, 299 PAK2, 12–13 PARP, 12–13, 221 PARP cleavage, 18 PCAF, 203
PDGF, 138
Pediatric tumors, 208 Perforin, 22, 248 PERP, 204 Phagocytosis, 13 Phosphatidylserine, 14 Phosphorylation, 27, 138 PI3-K, 221
PI-3 kinase, 43 PIDD, 204 PIP5K, 98
PKC, 138, 221, 314, 323 PKC_, 98
PLAD, 75 Plectin, 12–13 Polyglutamine, 114
Posttranscriptional events, 179 PPAR-L, 299
Preligand assembly, 75 Primary human cultures, 315 Procaspase-8, 8, 21, 120–121, 135 Procaspase-8 dimer, 123
Procaspase-9, 6
Procaspase-10, 8, 21, 135 Procaspase activation, 121 Prodomain, 5, 113, 115, 120 Proinflammatory cytokine, 116 Prostate cancer, 138, 281, 291 Protease domain, 113, 117, 121 Protein kinase, 221
Proximity, 121 PTEN, 47–48 Puma, 15, 27–28, 46 R
Rac, 14
RACK1, 95, 101 Radiation, 291 Raf, 221
RAIDD, 3, 17, 95, 97, 103 RANK, 134, 281
RANKL, 66, 70, 134, 176, 289 RAR, 189
Rb, 44 Reaper, 4–5
Receptor mutagenesis, 77
Receptor tyrosine kinases, 121, 233 RelA, 97, 101
RelA⫺/⫺, 100, 242 Reprimo, 204 Retinoids, 189 RHG proteins, 5, 11 Rho, 112
RING domain, 9–10, 101
RIP, 26, 85, 95, 97, 99–100, 102–103, 176, 324
RIP⫺/⫺, 99
RIP-deficient mice, 99 RNA binding proteins, 181 ROCK1, 12–13, 112, 115 Rsk, 221
S
S6 kinase, 47 SADS, 25
Sensitizing agents, 308, 314 Sensitizing tumor cells, 305 Sequestration, 239–240
Smac/DIABLO, 4–5, 10–11, 19, 52, 136, 139, 141, 233
Smac/DIABLO peptide, 141 Small-cell lung carcinoma, 216 Small molecule therapy, 332 SMase, 95
SODD, 24, 95, 98, 101, 238 SODD-deficient mice, 101 Spinocerebellar ataxia, 114 SR proteins, 326–327 STAT, 166, 244 STAT1, 233 STAT2, 233
STAT1-null cells, 167 Structure, 66
Structure of mammalian caspases, 113 Structure of TNFL, 69
Sunburn cells, 46
Supra-molecular assembly, 72 Survivin, 9, 139
SV40 T antigen, 203 Syk, 165
Synergy, 270 T
T2K, 95, 98, 100–101 T2K⫺/⫺, 100–101 T2K-deficient mice, 100 TAC1, 281
TACE, 164
TAJ/TROY, 89–90 TANK, 95, 98, 100 TANK⫺/⫺ mice, 100 Targeted transcription, 342 Targeted transduction, 340 Tazarotene, 191
Tazorac, 191 TBK, 100 TBK1, 98
T-cell leukemia, 153
TCR-mediated proliferation, 96 Telomerase, 343
hTERT, 343
hTERT promoter, 343 TGF-F, 48, 71
Therapeutic applications of TRAIL, 133 Therapeutic window, 43
Thyroid lymphoma, 154 TL1A, 102
TNF, 20, 22, 48, 94–95, 99, 101–102, 116–
117, 119–120, 133, 149, 163, 176, 339 TNF domain, 70
TNF gene therapy, 348 TNFL domain, 72 TNF ligand, 65
TNF-like molecule 1A, 94 TNFR, 116, 133, 163
TNFR1, 22–23, 94, 97–98, 100–102, 116, 119, 149, 163–164
TNFR2, 22–23, 97–98, 100, 163–164 TNF receptor promoters, 163 TNF receptor, 9, 65
Toll receptors, 20 TPA, 166, 193
TRADD, 25–26, 85, 95, 97–98, 101–103, 119–120, 209
TRAF1, 9, 87, 101
TRAF2, 9, 26, 87, 95, 97–103, 176
TRAF2⫺/⫺, 99
TRAF2-deficient macrophages, 99 TRAF2⫺/⫺ TNF⫺/⫺, 99
TRAF2⫺/⫺ TNFR1⫺/⫺, 99 TRAF4, 87
TRAF5, 99, 103 TRAF6, 87, 103 TRAF6⫺/⫺, 89 TRAFs, 65, 85
TRAIL, 8, 20, 22–23, 25, 29–30, 46, 50–51, 55, 66, 71, 75, 94, 99, 102, 117, 119–
120, 124, 133, 135–141, 168, 176, 196, 232, 263, 281, 339
TRAIL blockade, 140
TRAIL-deficient mice, 134, 140 TRAIL DISC, 119
TRAIL gene therapy, 345 TRAIL knockout mice, 134 TRAIL-negative cells, 140 TRAIL-R1, 22, 116, 134, 176
TRAIL-R2, 22, 116, 134, 175–176, 179 TRAIL-R2/KILLER, 116
TRAIL-R3, 22, 134, 176 TRAIL-R4, 22, 134, 176 TRAIL receptors, 134 TRAIL-resistant cancers, 140 TRAIL-transfected cells, 140 TRAMP, 232
TRICK2, 134, 232 TRID, 22–23, 134 Trimeric TRAIL, 135 TRUNDD, 22–23, 134
TSP1, 204
Tumor cell resistance, 223 Tumor surveillance, 247 TUNEL, 54
TWEAK, 71, 232 Tweak/Apo3L, 102
Type I cells, 21, 26, 119, 137 Type II cells, 21, 26, 119, 137, 211 Type II transmembrane proteins, 20 U
Ubiquitin ligases, 10 Usurpin, 117 V
VEGF, 45, 49, 54 Velcade, 49 W
WD repeats, 219 WD-40 repeats, 8 WSL-1, 232 X
XEDAR, 73–74, 88
XIAP, 3–4, 9–11, 19, 101–102, 139, 233, 328
Z
ZAP70, 165
Zinc-binding site, 69, 71 ZVAD, 19
