Index A A20, 67, 117 120, 146, 152, 153, 160 162, 166 171, 189 191 Acetylation, 6, 78, 260, 262 Actin filament, 78, 237, 238, 287 304 Actin nucleation, 288, 295, 296 Adaptive immunity, 188 189, 214 Adult neurogenesis, 243 Adult T-cell leukemia, 161 Affi nity chromatography, 17 29 Age-related macular degeneration, 242 Agrin, 313 320 AKT pathway, 96 101, 214, 233 235, 273 AP-1, 10, 201 Apoptosis, 28, 65, 79, 128, 143, 162, 164, 169, 170, 187, 188, 190, 213, 218, 222, 223, 227 229 Arsenite, 79, 80 Aschoff s rule, 261 Autophosphorylation, 49, 51, 52, 215, 222, 315 B Basic helix loop helix (bhlh) proteins, 120 122, 252, 259 Bayesian network, 4, 9 B cell, 161 163, 170, 186, 188 190, 198 B cell lymphomas, 119, 161, 189, 192 B lymphocytes, 71 72, 178 BMAL1, 252 254, 258 261 Bone tumor metastases, 199 C Ca2+, 52, 106, 201 203, 206, 261 262, 300 Caenorhabditis elegans, 329, 338 Calcineurin, 206 CaMKII, 261 262 Cancer-associated fibroblasts (CAFs), 240, 241 Cancer progression, 235, 239 241, 277 Cancer stem cells (CSCs), 11, 241 Canonical pathway, 11, 65, 160 163, 166, 167, 179, 198 Carcinogenesis, 120, 219 221, 226 228, 274 277, 279, 280 Cardiac muscle, 288, 289, 296 297, 304 Cardiomyopathy, 298 299 Casein kinase I, 50, 254 Caspase-8, 128, 169 171 Cathepsin K, 199 CD40, 129, 161 163, 188, 189, 199 202 CD134 antigen. See OX40L CDDO-Im, 275, 277 CD40 ligand, 129, 178, 188 Cell-free protein array, 43 57 Cell-free protein synthesis, 44, 46, 56, 57 Cell migration, 9, 237, 238, 241, 243, 244, 288, 289, 302 Centrosome, 165, 226 228 cgamp, 114 117 cgas. See Cyclic GMP-AMP synthase (cgas) Circadian clock, 251 262 Classical pathway, 64, 65 Springer Japan 2015 J.-i. Inoue, M. Takekawa (eds.), Protein Modifi cations in Pathogenic Dysregulation of Signaling, DOI 10.1007/978-4-431-55561-2 343
344 Index CLOCK, 252, 253, 258 260, 262 Collision, 81 86, 88 Collision radius, 83, 84 Combinatorial explosion, 88 Computational model, 67, 73, 98, 102 Computer simulation, 63 73, 78 Congenital myasthenic syndrome (CMSs), 317, 319 320 Cowden syndrome, 234 CRY, 252, 256 258, 260 Cyclic GMP-AMP synthase (cgas), 114 117 CYLD, 54, 55, 146, 163, 183, 189 192 Cysteine, 5, 118, 119, 219, 272, 280 Cysteine-rich domains (CRD), 131, 133 Cytokine, 65, 66, 114, 128, 145, 161, 178, 181, 184, 185, 198, 206, 212, 223, 280, 288, 289, 291, 302 Cytonemes, 289, 299 304 D Daily rhythms, 251 DAP12, 201 Daple, 239 Data assimilation, 9 Degradation, 19, 46, 47, 54, 64 67, 71, 128, 144, 160, 164, 167, 168, 170, 179 181, 183 185, 187, 198, 199, 214 218, 244, 255, 257 259, 261, 270 273, 277, 279, 280, 292, 293, 328 Denosumab, 203, 206 Deterministic simulation (DS), 78, 79, 81 86 Deubiquitinating enzyme (DUBs), 146, 179, 189 92, 337 Diabetes mellitus, 96, 234, 244 Diabetic retinopathy, 242 Diffusion coefficient, 65, 67 69, 71, 82, 83, 89 Diffusion equation, 82 Disrupted-in-Schizophrenia 1 (DISC1), 237, 238, 242, 243 DNA-binding, 114, 115, 120, 121, 218, 253, 259, 330 333, 336 Dok-7, 313 317, 319, 320 Dominant negative HLH (dnhlh) family, 120 123 DS. See Deterministic simulation (DS) Dynein, 80, 86, 89 DYRK1A, 256, 257 E EC 50, 96, 99, 101, 103, 105 EGFR. See Epidermal growth factor receptors receptor (EGFR) eif2α, 79, 80 ELK-1, 213, 218, 219 Epidermal growth factor (EGF), 4, 6 9, 11, 12, 21, 22, 25, 215, 239, 300 Epidermal growth factor receptors receptor (EGFR), 4, 6, 8, 9, 213, 215 217, 229, 234, 238, 239, 315 ErbB signaling, 6, 9, 13 Extracellular signal-regulated kinase (ERK), 25, 36, 38 39, 98, 106, 189, 212 221, 256, 260, 291 F FBXL3, 257, 258 FBXL21, 258 FcR γ, 201 Feed-forward (FF), 98 101, 103 105 Fibroblast growth factor (FGF), 7, 215, 289, 300 304 Filopodia, 78, 91, 289, 299, 302 Fluorescence microscope, 37, 38, 339 Förster (or fluorescence) resonance energy transfer (FRET), 33 40, 48 FRET biosensors, 33 36, 38, 39 G Gab2, 202, 203, 206 GADD45, 221 225 G α-interacting vesicle-associated protein, 239 Genotoxic stress, 190 Gipie, 239 Girdin, 233 244 Glucocorticoid-induced TNF receptor ligand (GITRL), 131 Glucose metabolism, 97, 101 103, 106, 291 Glycosylation, 78, 310, 319, 320 Green fluorescent protein (GFP), 31, 32, 36 GSK3β, 10, 97, 101, 104, 237, 257, 259, 273 H Helix-loop-helix (HLH) proteins, 120 123 Hemimegalencephaly, 235 Highly conserved domain in RANK (HCR), 200 206 Hodgkin lymphoma, 160 162, 168, 225 HOIL-1L, 145 150, 183, 187 189, 192 HOIL-1L-NZF, 147 150, 153 HOIP, 145, 183 187, 189 192 Homeodomain-interacting protein kinase 2 (Hipk2), 335, 336 Human homologue of murine maternal Id-like molecule (HHM), 120 123
I n d ex 345 I IGF-1. See Insulin-like growth factor 1 (IGF-1) I κb kinase (IKK), 64 68, 70 72, 117, 120, 144, 146, 160 162, 165 169, 179, 181, 184 186, 189, 191 IKK α, 64 66, 144, 160, 168, 179, 185, 199 IL-1β, 178, 181, 184 186, 188 Immobilized metal affinity chromatography (IMAC), 6, 18, 19 Immunodeficiency, 187 188, 192 Immunoreceptor tyrosine-based activation motif (ITAM), 201 Incoherent feed-forward loop (IFFL), 98, 99, 101, 104 106 Inflammation, 65, 128, 143, 160, 177, 181, 184, 187 188, 190, 192, 198, 281 Inhibitor of apoptosis, 181, 182 Inhibitor of kappa B (IκB), 64 68, 71, 117, 128, 144, 160, 168, 178, 179, 181, 184, 185, 198, 271 Innate immunity, 114, 184, 186 187 Insulin, 95 107, 234, 236, 291 Insulin-like growth factor 1 (IGF-1), 288 297, 304 Intercellular coupling, 261, 262 Interferon (IFN), 181, 186, 187 IFN-β, 114, 116 IFN-γ, 187, 223 Intracellular Ca2+, 261 J c-jun N-terminal kinase (JNK), 98, 170, 190, 212, 213, 218, 221, 222, 228, 260 261 Lymphoma, 119, 160 162, 164, 168, 170, 189, 192, 225 Lymphotoxin-α (LT-α), 129, 131, 133, 134, 136 Lys48-linked polyubiquitination, 198 M Mammalian target of rapamycin (mtor), 11, 12, 98, 236, 237, 243 MAPKs. See Mitogen-activated protein kinase (MAPKs) Mass spectrometric analysis, 259 mdia, 288, 302 MEKK1, 165, 213, 216, 218, 220, 221 Metabolomics, 26, 28, 97 Metal oxide affinity chromatography (MOAC), 18, 19 Mitogen-activated protein kinase (MAPKs), 10, 180, 181, 184, 186, 200, 201, 211 213, 216, 219, 222, 228, 229, 256 MKK4, 213, 214, 216, 221, 227, 228 Molecular hubs, 13 Motor neuron disorders, 320 Motor protein, 80, 81, 86, 89 MTK1, 213, 221 226 mtor. See Mammalian target of rapamycin (mtor) Multiple myeloma, 7, 161 164, 167, 203 Muscle hypertrophy, 289 293 Muscle-specific receptor tyrosine kinase (MuSK), 310, 312 320 Myasthenia gravis, 317, 318 Myofibrils, 287 304 Myopathy, 289, 298 L Lef1, 330 339 Linear ubiquitin chain assembly complex (LUBAC), 117, 120, 145, 146, 149, 183 189, 191, 192 Linear ubiquitin chains, 170, 182 184 Lipoprotein receptor-related protein 4 (Lrp4), 314 316, 318, 320 Liquid chromatography-tandem mass spectrometry (LC-MS/MS), 4, 6 LIT-1, 329, 338 LUBAC. See Linear ubiquitin chain assembly complex (LUBAC) Lymphoid malignancies, 159 171 N Nebulette, 296, 297 Nebulin, 288, 289, 293, 294, 297 Negative feedback, 14, 72, 105, 117, 160, 168 169, 252 NEMO, 65, 117, 120, 144 146, 150, 152, 160, 165 168, 179, 181, 183 187 Nemo-like kinase (NLK), 329 335 NEMO-UBAN, 146, 150 153 Network analysis, 3 13 Neurodegenerative diseases, 18, 28, 177, 213, 236 Neuromuscular disorder, 317, 320 Neuromuscular junction (NMJ), 309 321
346 Index NFATc1, 201, 202, 206 NF- κb oscillation, 63 73 pathway, 116 118, 143 153, 178 186, 188, 191, 198 signaling, 6, 9, 13, 73, 144 146, 150, 153, 159 171, 179 184, 189 192, 197 206 NF- κb-inducing kinase (NIK), 64, 66, 160 165, 167 170, 179 NLK. See Nemo-like kinase (NLK) Nlk2, 331 334, 338, 339 NMJ. See Neuromuscular junction (NMJ) NOD, 178 Non-canonical pathway, 65, 160 164, 166 168, 178, 179, 188, 198 Non-classical pathway, 64, 66 Notch-regulated ankyrin repeat protein (Nrarp), 336 339 Npl4 zinc-finger (NZF ), 145 150, 181 183 N-WASP, 288, 289, 293 299, 302, 304 O O-GlcNAcylation, 260, 262 Oligodendrocyte transcription factor (Olig1), 120 123 Oltiplaz, 274 Oltipraz, 274 Organelles, 64 66, 68, 71, 78, 91, 299 Oscillations, 63 73, 201, 251 262 Osteoclast, 199 206 Osteoclastogenesis, 197 206 Osteopetrosis, 199, 200 Osteoporosis, 199, 203, 206, 327, 339 OTM:d2EGFP, 338, 339 OTU deubiquitinase domain, 117 OTULIN, 146, 183, 189 191 OX40L, 130, 131 P p50, 64 66, 143, 159, 178, 184, 185, 198, 199 p52, 64 66, 159, 166 168, 178, 179, 198, 199 p100, 64 66, 159, 163, 166 168, 178, 179, 198, 199 p105, 65, 159, 178, 198 Paget s disease, 199, 203, 206 Paladin, 235, 243 PAMPs. See Pathogen-associated molecular patterns (PAMPs) Partial least squares regression (PLSR), 4, 9 Pathogen-associated molecular patterns (PAMPs), 114, 178, 186 PC12 pheochromocytoma cells, 38 PER2, 252, 254 256, 260, 261 Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), 54, 55, 234, 273, 280 Phospholipase Cγ 2 (PLCγ2), 201 203, 206 Phosphoproteome, 4, 6 13, 17 29 Phosphoproteome dynamics, 4, 8, 9, 11, 13 Phosphoproteomics, 3 13, 26, 28 Phosphorylation, 3, 6 12, 17, 31, 43, 51 52, 66, 78, 97, 114, 128, 144, 160, 178, 198, 212, 235, 239 241, 253, 280, 291, 310, 327 Phos-tag, 17 29, 49, 52 PI3K, 217, 233, 234, 236 238, 273, 288, 289, 291 293, 295, 303, 304 Polo-like kinase 4 (PLK4), 226 228 Poly-ubiquitin (Ub) chains, 52 54, 56, 143 146, 179 181, 183, 186, 190 192, 214, 271 POP-1, 329, 338 Postnatal angiogenesis, 240 242 Pre-ligand-binding assembly domain (PLAD), 131, 137, 138 Prion-related domain (PRD), 79, 80, 88 Proteasome, 11, 44, 56, 167, 168, 170, 180, 244, 271, 293, 336, 337 Protein kinase C, 106, 259, 260 Protein protein interaction analysis, 47 55 Protein stabilization, 258, 339 Proteomics, 4 8, 11, 12, 18, 19, 51, 338 Pulse stimulation, 98 100, 102 104 Q Quantitative proteomics, 5, 8 R Ramp stimulation, 98 100, 102 104, 107 Random walk, 81 83, 85, 87 RANK, 162, 199 206 RANKL, 199, 201, 203, 205, 206 Rapsyn, 317, 319 Ras, 212 215, 217, 218, 220, 221, 291 Reaction probability, 82, 84, 85 Receptor for activated C kinase-1 (RACK1), 260 Receptor-interacting protein 1 (RIP1), 117, 120, 144 146, 170, 184, 187, 189 Receptor tyrosine kinase (RTKs), 213, 215 217, 234, 236, 310, 312, 314, 315, 320
Index 347 Retinopathy of prematurity, 242 Rev-Erb, 252, 253 Rheumatoid arthritis, 128, 192, 199, 203, 206 RhoD, 289, 300 304 RNA recognition motifs (RRM), 79 ROR, 252, 253 RTKs. See Receptor tyrosine kinase (RTKs) S SAPK. See Stress-activated protein kinase (SAPK) Scaffold protein, 165, 181, 216 218 Schizophrenia, 235 SHARPIN, 120, 145, 146, 149, 183, 187, 188, 192 SH3 domain, 294 298, 304, 317 Shotgun proteomics, 5 7, 11, 19 Single-cell monitoring, 262 Skeletal muscle, 288 290, 293 296, 298, 304, 310 313, 317, 318, 320, 321 Smad, 120, 216, 223 225 Small GTPases, 36, 39, 288, 316 Small ubiquitin-like modifier (SUMO), 219 221 Spatial parameters, 63 73, 89 Src kinase, 239 Stable Isotope Labeling by Amino acids in Cell culture (SILAC), 5 Step stimulation, 98, 99, 104 Stimulator of interferon genes (STING), 114 117 Stochastic jump, 81 Stochastic simulation, 67, 77 92 Stress-activated protein kinase (SAPK), 212, 221 228 Stress granule, 77 92 Systems biology, 40 T TAB2-NZF, 145, 147 149 Tartrate-resistant acid phosphatase (TRAP), 199, 204 206 Tax, 164 169 T cells, 6, 128, 160, 161, 164 167, 188, 202, 277, 314, 315, 320 Tcf/Lef, 327 340 Temporal patterns, 96 97, 100 107 3D model, 68, 71 Thrombospondin 1 (TSP-1), 224, 225 TIA-1, 79, 80, 87 89 Time constant, 96, 98, 99, 101, 103, 105 TLR. See Toll-like receptors (TLR) TNF like ligand 1A (TL1A/VEGI), 129 TNFR-associated factor 2 (TRAF2), 64 66, 138, 145, 161, 163, 164, 167, 169, 170, 181, 184 TNFR-associated factor 6 (TRAF6), 53, 65, 66, 138, 139, 145, 161, 165, 170, 181, 184, 186, 200 203, 206 TNF receptor, 65, 129, 131, 132, 144, 161, 163, 178, 181, 184, 185, 188, 191, 199 TNF receptor-associated factor (TRAF), 65, 66, 117, 181, 184, 200 TNF receptor superfamily (TNFRSF), 178, 185, 188, 199, 200 TNF receptor superfamily member 1A (TNFR1; CD120A), 128, 129, 132 137, 184 TNF receptor superfamily member 1B (TNFR2; CD120B), 128, 129, 131 138, 184 TNF-related apoptosis-inducing ligand (TRAIL), 129, 169, 170 TNFR signaling complex, 117, 118, 120 Toll-like receptors (TLR), 168, 178, 181, 186 TOPdGFP, 331 333, 336, 339 TRAF2. See TNFR-assosicated factor 2 (TRAF2) TRAIL-DR5, 131 Transforming growth factor (TGF)-β, 120, 179, 223 225 Transgenic mice, 40, 161, 254, 276, 298 Transposase-mediated gene transfer, 40 True intracellular space (TiCS), 73 Tuberous sclerosis complex 2 (TSC2), 236, 237, 291, 293 Tumor microenvironments, 161, 240, 241 Tumor necrosis factor (TNF) TNF-α, 64, 65, 120, 144, 146, 169, 178, 184 187, 189, 190, 212 TNF-β, 129, 130 Tumor necrosis factor ligand superfamily member 2, 127 Type I collagen, 199 U UBAN. See Ubiquitin binding in ABIN and NEMO (UBAN) Ubc9, 215, 219 221 UBDs. See Ubiquitin-binding domains (UBDs)
348 Index Ubiquitin, 43 57, 67, 117, 119, 143 153, 160, 166, 169 171, 179 187, 189 192, 214 219, 255, 257, 258, 271 273, 279, 293, 320, 336, 337 Ubiquitination, 6, 43, 44, 52 57, 78, 138, 144, 146, 160, 165, 166, 169, 177 192, 214, 217, 255, 257, 258, 260, 262, 272, 277, 310, 328, 329, 336 338 Ubiquitin-binding domains (UBDs), 52, 143 153, 179 186 Ubiquitin binding in ABIN and NEMO (UBAN), 146, 186 V Vav3, 203 W Wheat cell-free system, 53, 57 Wnt/β-catenin signaling, 327 340 Z Z-bands, 288, 293 298 Zinc finger, 114 120, 138, 145, 146, 169, 170, 182, 183, 189, 191