Advances in Enzyme Regulation 51 (2011) 320–329

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advenzreg

Subject index volume 51

Achilles’ heel cancer, targeting the cancer initiating cell of, 152–160effects of cytotoxic effects of docetaxel on CICs by combination with targeted therapies and naturalproducts, 159–160natural products-dietary supplements and prostate cancer, 155–156prostate cancer, 153prostate cancer and radiation therapy, 153prostate cancer therapy, 153side effects of radio and chemo-therapies–induction of signaling pathways, 153–154targeting signal transduction pathways in prostate cancer, 154–155

Aktactivated in leukemia cell survival, 38–40, 42–44regulates de novo lipogenesis though activation of SREBP and its target genes, 196–200, 203–205role in deciphering the signaling pathways of cancer stem cells of GBM, 164–169

Apoptosis, p53 and ceramide have been shown to regulate, 220–226AP sites, form when the reaction of hydrogen peroxide with DNA causes bases, 264–265Arachidonic acid, well known chemoattractant for phagocytes, 59Archaea, synthesis and use of Ins in, 84–89

Bacteria, inositol in, 84–89B cell survivalregulation by inositol 1,4,5-trisphosphate 3-kinase B, 66–68, 70–71regulation by inositol 1,4,5-trisphosphate 3-kinase B inIns(1,4,5)P3 3-kinases, 67–68mechanisms of Ins(1,3,4,5)P4 action, 68, 70

Biosynthesis, of archaetidylinositol, 84, 87Bone marrow transplantation, of weeble fetal liver cells into lethally irradiated wild type mice, 103

Cancer, overexpression or over-activity of ChoKa but not ChoKb in, 188–191Cancer initiating cell, targeting the Achilles' heel of cancer, 152–160effects of cytotoxic effects of docetaxel on CICs by combination with targeted therapies and naturalproducts, 159–160natural products-dietary supplements and prostate cancer, 155–156prostate cancer, 153prostate cancer and radiation therapy, 153prostate cancer therapy, 153side effects of radio and chemo-therapies-induction of signaling pathways, 153–154targeting signal transduction pathways in prostate cancer, 154–155

Cancer stem cells, promote differentiation into more mature prostate cancer cells, 152, 158Cell-signaling, functions of the PPIP5Ks, 15

0065-2571/$ – see front matterdoi:10.1016/j.advenzreg.2011.03.001

Subject Index / Advances in Enzyme Regulation 51 (2011) 320–329 321

Ceramideregulates cell cycle arrest, senescence, and apoptosis, 220–226role in signal transduction and cellular function., 229–231, 233, 238–239, 241–243sphingomyelinases mediate the hydrolysis of sphingomyelin in production of, 51, 54, 56

Chemotherapeutic drugs, for treatment of prostate cancer, 156–160Chimeric mice, role of inositol polyphosphate 4-phosphatase 1 in platelet function using, 103–104Choline kinase (E.C.2.7.1.32), alpha and beta, in carcinogenesis, different role in lipid metabolism andbiological functions, 183–184, 186–191biochemical characterization of ChoK isoforms, 184, 186–187ChoK and lipid metabolism, 184, 186differential role between ChoK isoforms in cell transformation and tumorigenesis, 187–189genes encoding choline/ethanolamine kinases, 183–184regulation of ChoK activity, 187specific inhibition of ChoKa, 189–190

Choline kinase inhibitors, with potential antitumoral activity, 189–191Chromatin, important regulators of gene expression, 118, 120–121Chromatin fibers, studies of DNA and, 259, 267–269Chromatin immunoprecipitation, YBX1 targets identified in colorectal cancer cells by, 133–134Chromatin organization, pathogenesis of muscular laminopathies associated with, 251CK2 (EC 2.7.11.1)impact of PTEN regulation on PI3 K-dependent signaling and leukemia cell survival, 37–44on PI3 K-dependent signaling and leukemia cell survival, impact of PTEN regulation byhighly oncogenic non-oncogene, in tumorigenesis and leukemia, 40–41

Class I PI3Ks, signalling via, 27–29, 31–33Colitis, effects of BLT2-deficiency in, 61Colorectal cancer, role of YBX1 as a prognostic factor in, 129–130, 132–135

Diphosphoinositol polyphosphatesmolecular mechanisms of, 13–20, 22phospholipase C-initiated synthesis ofmetabolism of, 13–15protein phosphorylation by, 19–20, 22receptors for, 17–18signaling by, 15–17

DNA damage, p53-dependent apoptosis occurs secondary to, 220, 222–225DNA damage response-associated proteins, role of Fhit proteins in, 210, 212, 215DNA fibers, analysis of DNA repair on, 259–268DNA repair, on DNA fibers, 258, 263, 265DNA replication, temporal and functional analysis in early S phase, 257–270analysis of, 259–263analysis of chromatin structure and dynamics of DNA replication, 268–269analysis of DNA repair on DNA fibers, 263–266genomic and temporal mapping of DNA replication origins activated early in S phase, 266–268studies of DNA and chromatin fibers, 259

Drug design, of phosphoinsitide-3-kinase, 273–278activation by phosphotyrosine peptide (pY-pep) binding, 275cancer-associated mutations, 276–277structure of the p110a/niSH2 complex of PI3 Ka, 275

Early S phase, temporal and functional analysis of DNA replicated in, 257–270analysis of, 259–263analysis of chromatin structure and dynamics of DNA replication, 268–269analysis of DNA repair on DNA fibers, 263–266genomic and temporal mapping of DNA replication origins activated early in S phase, 266–268studies of DNA and chromatin fibers, 259

Subject Index / Advances in Enzyme Regulation 51 (2011) 320–329322

EDMD see Emery-Dreifuss muscular dystrophyEicosanoids, 12-HHT was originally identified as a by-product of thromboxane A2 biosynthesis, 61Emery-Dreifuss muscular dystrophy (EDMD), caused by LMNA mutations, 248, 250, 253EMT see Epithelial-mesenchymal transitionEpigenetics, mechanisms involved in RAS target deregulation, 127, 129, 134Epithelial to mesenchymal transition (EMT)mechanism of contribution of ILK froma3b1integrin-dependent adhesion on laminin 5 stimulates Akt kinase activity through ILK,198–199decreases transcriptional activity of b-catenin and NF-kb, 200–201knockdown is sufficient to activate GSK-3b, 199–200regulates cell migration and invasion, 202regulates level of cytosolic pool of b-catenin, 200silencing of ILK affects N-cadherin expression, 201–202siRNA-mediated knockdown of ILK results in decrease of Akt kinase activity, 199

mechanism of contribution of ILK to, 195–203, 205–206Eukaryotic gene expression, control of gene loops and transcriptional memory, 118–124characteristics of, 120–121chromosome conformation capture, 120dependent upon components of promoter and terminator complexes, 121genetic suppression and discovery of, 118–119Ssu72 is an integral component of the CPF 30-end processing complex, 120Ssu72 is a Pol II CTD phosphatase, 119–120TFIIB at the terminator, 121–122

Evolution, and functions of inositol and derivatives, 84–89all eukaryotes use inositol lipids, 88–89archaeal synthesis and use of, 85–87in bacteria, 87–88

Fatty acid, LTB4, derived from arachidonic acid, 59, 61Fragile histidine triad proteins, are members of the histidine triad gene/gene product family, 208–215human FHIT locus, 211Hydrolase activity, 211interactors, 212–213role in DNA damage response, 212role in oxidative and replicative stress, 211–212

Function, regulation and roles of PI3 Kb, major actor in platelet signaling and, 106–114atypical class IA PI3 K, 108–109cell types, 113–114G-protein-coupled receptors, 110–111integrin aIIbb3, 111–113stimulated by von Willebrand factor and collagen, 109

GBM see Glioblastoma multiformeGene expression profiling, for fibroblasts, epithelial cells and other cell types, 126–127, 133–135Gene loop, and transcriptional memory, control of eukaryotic gene expression, 118–124characteristics of, 120–121chromosome conformation capture, 120dependent upon components of promoter and terminator complexes, 121genetic suppression and discovery of, 118–119Ssu72 is an integral component of the CPF 30-end processing complex, 120Ssu72 is a Pol II CTD phosphatase, 119–120TFIIB at the terminator, 121–122

Gene silencing, difference in tumor size was due to, 131, 135Glioblastoma multiforme (GBM), deciphering the signaling pathways of cancer stem cells of, 164–169GPCR see G protein coupled receptor

Subject Index / Advances in Enzyme Regulation 51 (2011) 320–329 323

G protein coupled receptor (GPCR)is a low-affinity LTB4 receptor, 60, 62PDZ domain proteins play a pivotal role in, 139–148

Hair cells, of inner ear, highly specialized cells to transduce auditory signals, 172, 175, 177, 180Histidine triad proteins, Hint and Fhit proteins are members of, 208–215, 210–211Aprataxin, 210Hint1, 210Hint2, 210–211

ILK see Integrin linked kinaseImmunology, biological roles of LTB4 and its receptors in, 59–6312-HHT is an intrinsic ligand for BLT2, 61molecular identification of BLT1 and BLT2, 59–60roles of BLT2 in protecting intestinal inflammation, 61roles of BLT1 in T cells, dendritic cells, and osteoclasts, 62

Inflammation, roles of BLT2 in protection of, 61–62Inositides, signaling in regulation of cell cycle progression, 2–3, 5, 7, 9Inositol, for the generation of a multitude of signaling molecules, 74–81Inositol hexakisphosphate kinase (IP6K), signaling role of, 74–81inositol pyrophosphate mechanism of action, 78–79inositol pyrophosphate regulated functions, 79–80PP-IP5 kinases, 76regulation of cellular inositol pyrophosphate levels, 76–78

Inositol (Ins), and derivatives, evolution and functions of, 84–89all eukaryotes use inositol lipids, 88–89archaeal synthesis and use of, 85–87in bacteria, 87–88

Inositol phosphate, membrane-anchored inositol lipids and the cytosolic, 66, 68, 71Inositol polyphosphate 4-phosphatase 1, role in platelet function using a weeble mouse

model, 101–104Inositol pyrophosphates, protein pyrophosphorylation by, 14Inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), role in B cell survival, development and function, 66Inositol 1,4,5-trisphosphate 3-kinase B (Itpkb), regulation of B cell survival, development and function

by, 66–68, 70–71Ins(1,4,5)P3 3-kinases, 67–68mechanisms of Ins(1,3,4,5)P4 action, 68, 70

Ins see InositolIns(1,3,4,5)P4 see Inositol 1,3,4,5-tetrakisphosphateIntegrin linked kinase (ILK), mechanism of contribution to EMT, 195–203, 205–206a3b1integrin-dependent adhesion on laminin 5 stimulates Akt kinase activity through ILK, 198–199decreases transcriptional activity of b-catenin and NF-kb, 200–201knockdown is sufficient to activate GSK-3b, 199–200regulates cell migration and invasion, 202regulates level of cytosolic pool of b-catenin, 200silencing of ILK affects N-cadherin expression, 201–202siRNA-mediated knockdown of ILK results in decrease of Akt kinase activity, 199

IP7, able to transfer the b-phosphate to prephosphorylated proteins, 74–80IP6K see Inositol hexakisphosphate kinaseISC1, serves to function as a binding domain for anionic phospholipids, 51–54Itpkb see Inositol 1,4,5-trisphosphate 3-kinase B

Kinase, over-expressed in yeasts, 13–15, 18–20

Laminopathies, role of prelamin A in, 246–254altered signalling in muscular laminopathies, 249–250

Subject Index / Advances in Enzyme Regulation 51 (2011) 320–329324

mechanisms of skeletal myogenesis and muscle regeneration, 248–249modulation of expression of nuclear envelope and nuclear lamina proteins during myogenesis, 249muscular laminopathies, 248pathogenic mechanism in lipodystrophic laminopathies, 247–248pathogenic mechanism in progeric laminopathies, 247pathogenic mechanisms of muscular laminopathies, 250–251role of, 251–252

Leukemia, involvement of PI3K signaling pathway in, 37–44Leukotriene B4 receptors, novel roles in immunological regulations, 59–6312-HHT is an intrinsic ligand for BLT2, 61molecular identification of BLT1 and BLT2, 59–60roles of BLT2 in protecting intestinal inflammation, 61roles of BLT1 in T cells, dendritic cells, and osteoclasts, 62

Lipid kinasefrequently mutated in several cancer, 273signalling in the nucleus, 91–97

Lipid phosphate phosphohydrolase, are lipid phosphatases with broader substrate specificity, 236–237Lipid signaling subcellular localization, affects downstream metabolism of sphingosine- 1-phosphateand access of sphingosine kinase to its substrates, 243

Mammalian target of rapamycin (mTOR), role in deciphering the signaling pathways of cancer stemcells of GBM, 164–169MAPK see Mitogen-activated protein kinaseMDS see Myelodysplastic syndromesMelanoma, mechanism of ILK signaling in, 195–196, 198–206Mice, presenting a genetic inactivation of PI3Kb, 106, 108–110, 112–113Microarray analysis, standard approach for identifying transcriptional targets of the RAS pathway,126–127, 130, 133–134Microvilli, interaction of PLCd3 with Myo6 is functional for maintenance of, 172, 174–175, 178–180Mitogen-activated protein kinase (MAPK), role in deciphering the signaling pathways of cancer stemcells of GBM, 164–169MTOR see Mammalian target of rapamycinmTORC1, second kinase complex containing mTOR as its catalytic subunit, 282–284, 287–289Muscle regeneration, involves the activation of muscle satellite cells, 248–250, 254Mycobacterium, Ins lipids were discovered in, 87–88Myelodysplastic syndrome (MDS), role of nuclear PLCb1 in, 3, 7–9Myogenesis, modulation of expression of nuclear envelope and nuclear lamina proteins during,248–253Myosin VI, on plasma membrane, phospholipase C novel binding partner of, 171–175, 177–178, 180expression of Myo6 was decreased in intestine of PLCd3KO mice, 178identification of Myo6 as a PLCd3 interacting protein, 174, 176PLCd3 and Myo6 confined to be co-expressed in the hair cells of the inner ear, 175, 176, 177–178PLCd3 has an essential role for development of microvilli architecture in Caco-2 colonic carcinoma

cell line, 178, 179, 180tail domain of Myo6 is sufficient for binding to the PH domain and C2 domain of PLCd3, 175, 176

Myotubes, cell population undergoes differentiation to form, 248–250, 252–253

N-cadherin, onmelanoma cells plays a dual role promoting tumorigenesis, 195–197, 201–203, 205–206Nestin, in GBM, mTOR and MAPK increased the expression of, 166–169Neutral sphingomyelinase-2 (nSMase2), phosphoprotein regulated by calcineurin, 51–56Neutral sphingomyelinase (N-SMases)considered to be key mediators of stress-induced ceramide productioncellular compartmentalization, 56ion dependency, 53P-loop-like domain, 54

Subject Index / Advances in Enzyme Regulation 51 (2011) 320–329 325

regulation by anionic phospholipids, 53–54regulation by interacting proteins, 55–56regulation by phosphorylation, 54–55

key mediators of stress-induced ceramide production, 51–57domain structure, 52

Nitrilase family proteins, consist of thiol enzymes involved in natural product biosynthesis, 208–215NSMase2 see Neutral sphingomyelinase-2N-SMases see Neutral sphingomyelinaseNuclear, phosphoinositide signalling in, 91–97PtdIns(4,5)P2, 93–94PtdIns5P, 95–97specific regulators of PtdIns(4,5)P2 synthesis, 94–95

Nuclear envelope, roles inmyoblast differentiation and/ormusclemaintenance, 246–247, 249, 251–253Nucleus, PLCb1 translocates to, 2–7, 9Nulcear lamina, modulation of expression of nuclear envelope and, 249, 253

Oncogene, CK2 plays a major role in tumorigenesis by enhancing the transforming potential of, 39–41Origins of DNA replication, identification of, 259, 267Ovarian carcinoma, regulation of HMGA2 gene in, 130–131

p53, and regulation of bioactive sphingolipids, 219–226ceramide, 220–221glycosphingolipids, 221sphingolipid metabolizing enzymes, 221–223sphingolipids in animal models, 224tumor cell senescence, 224tumor cell senescence as chemotherapeutic mechanism, 225tumor suppressor protein, 219–220

p85a, oncogenic mutations occur at the interfaces between, 273–278p110a, oncogenic mutations occur at the interfaces between, 273–278p110a/p85a, breaks the interaction of ABD with iSH2 domain of p85, 276–277PDZ-binding motif, protein interaction motif responsible for subtype-specific regulation of PLC-b, 141–144, 146, 148PDZ domain proteinsubtype-specific role of phospholipase C-b via differential interactions withdomain structures and the regulation of PLC-b subtypes by G proteins, 140NHERF, 142–143Par-3, 145PDZ-binding motif, 141potential PDZ domain proteins that interact with PLC-b subtypes and GPCRs, 146–147PSD-95, 145–146role of PDZ domain proteins in subtype-specific role of PLC-b in GPCR-mediated signaling,141–142Shank2, 143–145

subtype-specific roles of phospholipase C-b via differential interactions with, 138–148PHD finger, generally only found in nuclear proteins, 95–96Phosphatidylcholine (PC), major phospholipid in eukaryotic membranes, 183–184, 186Phosphatidylethanolamine (PE), ChoK enzymes involved in the synthesis of, 183–184Phosphatidylinositide-3-kinases (PI3K), design of mutation specific inhibitors of, 273–278activation by phosphotyrosine peptide (pY-pep) binding, 275cancer-associated mutations, 276–277structure of the p110a/niSH2 complex of PI3Ka, 275

Phosphatidylinositol-(3,4,5)-triphosphate (PtdIns(3,4,5)P3), major output signal from the class I PI3Ks,27, 30–33

Phosphoinosite-3,4,5-triphosphate (PIP3), act as membrane docking sites for pleckstrin homologydomain, 273–274

Subject Index / Advances in Enzyme Regulation 51 (2011) 320–329326

Phosphoinositide 3-kinase beta (PI3Kb), major actor in platelet signaling and functions, regulation androles of, 106–114atypical class IA PI3K, 108–109cell types, 113–114G-protein-coupled receptors, 110–111integrin aIIbb3, 111–113stimulated by von Willebrand factor and collagen, 109

Phosphoinositide 3-kinase (PI3 K) (E.C.2.7.1.153)class IA, signalling via, 27–33barriers to progress, 33degradation of PtdIns(3,4,5)P3 signals, 31issue of the existence of multiple molecular species of phosphoinositides, 30–31outputs from, 31past work, 28–29potential molecular explanations for the phenomenon of class IA PI3K isoform specificity, 32–33problems faced in explaining isoform specific class IA PI3K signalling on the basis of our currentunderstanding of the pathway, 31–32regulators of Class IA PI3 K activity, 29–30translation of PtdIns(3,4,5)P3 signals, 31

signaling and leukemia cell survival, impact of PTEN regulation by CK2 on, 37–44Phosphoinositide metabolism, phospholipase Cd3 is a key enzyme in, 171, 180Phosphoinositidesgenetic disruption of PI3-K unsuitable to distinguish the contributions of, 102signalling in the nucleus, 91–97PtdIns(4,5)P2, 93–94PtdIns5P, 95–97specific regulators of PtdIns(4,5)P2 synthesis, 94–95

Phospholipase C (PLC)enzyme responsible for hydrolysis, 138–148nuclear, physiology and pathology of, 2–9nuclear PLCb1 and cell cycle, 2–5

physiology and pathology of nuclearnuclear PLCb1 and myelodysplastic syndromes, 7–9nuclear PLCb1 during cell differentiation, 5–7

Phospholipase C (PLC) (E.C.3.1.4.11), novel binding partner of myosin VI on plasmamembrane,171–175,177–178, 180expression of Myo6 was decreased in intestine of PLCd3KO mice, 178identification of Myo6 as a PLCd3 interacting protein, 174, 176PLCd3 and Myo6 confined to be co-expressed in the hair cells of the inner ear, 175, 176, 177–178PLCd3 has an essential role for development of microvilli architecture in Caco-2 colonic carcinoma

cell line, 178, 179, 180tail domain of Myo6 is sufficient for binding to the PH domain and C2 domain of PLCd3, 175, 176

Phospholipids, present in and are made by most Archaea and all eukaryotes, 84–87, 89Phosphorylation, of proteins by diphosphoinositol polyphosphates, 13, 19–20, 22PI3 K see Phosphatidylinositide-3-kinasesPI3 Kb see Phosphoinositide 3-kinase betaPI3Ks see Phosphoinositide 3-kinasesPIP3 see Phosphoinosite-3,4,5-triphosphatePlatelets, major actor in signaling and functions in, regulation and roles of PI3 Kb, 106–114atypical class IA PI3 K, 108–109cell types, 113–114G-protein-coupled receptors, 110–111integrin aIIbb3, 111–113stimulated by von Willebrand factor and collagen, 109

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PLC see Phospholipase CPosttranslational regulation, of PTEN, importance in leukemia, 40Prelamin A, role in early steps of muscle differentiation, 246–254altered signalling in muscular laminopathies, 249–250mechanisms of skeletal myogenesis and muscle regeneration, 248–249modulation of expression of nuclear envelope and nuclear lamina proteins during myogenesis, 249muscular laminopathies, 248pathogenic mechanism in lipodystrophic laminopathies, 247–248pathogenic mechanism in progeric laminopathies, 247pathogenic mechanisms of muscular laminopathies, 250–251role of, 251–252

Promoter analysis, suggested a role of MAPK pathway and NFY transcription factors in regulatingCCNB1 expression and activity, 133Prostate cancer, second most prevalent cancer affecting men after lung cancer, 153–158, 160Proteomic, study of protein component of an organism, cell or tissue, 292–302p70S6 K, TPA induced activation of, 167–169Pta1, another component of the CPF complex and interacts directly with Ssu72, 121PtdIns(3,4,5)P3 see Phosphatidylinositol-(3,4,5)-triphosphatePTEN (EC 3.1.3.67), regulation by CK2, impact on PI3K-dependent signaling and leukemia cell survival,37–44

Pyrophosphate, of IP7 is able to transfer the b-phosphate to prephosphorylated proteins, 74–81Pyrophosphorylation, in which phosphate group is added onto pre-existing phosphoserine, 79

Radiation therapy, for treatment of prostate cancer, 153–154, 156, 158RAS targets, mediated deregulation of the transcriptome, 126–127, 129–135effects of MAPK signaling and epigenetic events on down-regulation of HLA class I and NKG2Dligands, 129–130heterogeneous and common patterns of transcriptional responses to, 126–127, 128high mobility AT-hook 2, 130–131YBX1, 131–134

Reactive oxygen species (ROS), radio- and chemotherapy will result in generation of, 153Receptor tyrosine kinase, cell surface receptors involved in signal transduction, 292–302dimerization/activation, 294–297introduction to proteomic analyses, 293–294phosphoproteomics, 297–301role of other PTMs in cell signaling, 301–302

Regulationof the eukaryotic N-SMase family members, 52–56regulation and roles of PI3 Kb, major actor in platelet signaling andatypical class IA PI3 K, 108–109

and roles of PI3Kb, major actor in platelet signaling and functions, 106–114cell types, 113–114G-protein-coupled receptors, 110–111integrin aIIbb3, 111–113stimulated by von Willebrand factor and collagen, 109

ROS see Reactive oxygen species

Senescence, p53 and ceramide have been shown to regulate, 219–220, 224–226Signaling, role of inositol hexakisphosphate kinases, 74–81inositol pyrophosphate mechanism of action, 78–79inositol pyrophosphate regulated functions, 79–80PP-IP5 kinases, 76regulation of cellular inositol pyrophosphate levels, 76–78

Signaling pathways, are the activation/deactivation of transcriptional regulators, 292–294, 296–298,300–302

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Signal transductionof phosphoinositide 3 kinase in leukemia, 38RAS-dependent, role of E2F transcription factors in, 129, 132

Signal transduction inhibitors, effects on prostate cancer initiating cell, 154–156, 158S6 K see S6-kinaseS6-kinase (S6 K), required to facilitate the elongation step of protein translation, 280–285, 287–288combined silencing of S6K1 and S6K2 does not prevent Akt dependent accumulation of mature

SREBP, 284–285genetic deletion of both S6K1 and S6K2 does not prevent accumulation of matureSREBP, 285, 287–288

Sphingolipid metabolism, sphingosine kinase localization in the control of, 229, 231–239, 241–243contructs of sphingosine kinase localized to specific intracellular compartments, 233degradation of S1P preferentially affects the secreted pool of S1P, 236–237dictates utilization of dihydrosphingosine as a substrate, 238–239, 241–242non-specific lipid phosphatases preferentially utilize S1P generated at the plasma membrane,237–238

Sphingolipidsbioactive, p53 and regulation of, 219–226ceramide, 220–221glycosphingolipids, 221sphingolipid metabolizing enzymes, 221–223sphingolipids in animal models, 224tumor cell senescence, 224tumor cell senescence as chemotherapeutic mechanism, 225tumor suppressor protein, 219–220

SMase is important for local regulation of, 55–56Sphingosine kinase, localization in the control of sphingolipid metabolism, 229, 231–239, 241–243contructs of sphingosine kinase localized to specific intracellular compartments, 233degradation of S1P preferentially affects the secreted pool of S1P, 236–237dictates utilization of dihydrosphingosine as a substrate, 238–239, 241–242non-specific lipid phosphatases preferentially utilize S1P generated at the plasmamembrane, 237–238

Sphingosine kinase (E.C.2.7.1.91), a sphingolipid metabolizing enzyme act as oncogene, 219, 224Sphingosine-1-phosphate, are critical signaling components in vascular biology, tumorogenesis,inflammation, and immune function, 229–232, 235, 238, 240, 243Sphingosine-1-phosphate lyase, S1P is the substrate for, 231–232SREBP see Sterol regulatory element binding proteinsSsu72, plays key role early in the transcription cycle, 119–123Sterol regulatory element binding proteins (SREBP), are expressed as inactive precursors and reside asintegral transmembrane proteins, 280–285, 287–288combined silencing of S6K1 and S6K2 does not prevent Akt dependent accumulation of matureSREBP, 284–285genetic deletion of both S6K1 and S6K2 does not prevent accumulation of mature SREBP, 285, 287–288

Subtype-specific role, of phospholipase C-b via differential interactions with PDZ domainproteins, 138–148domain structures and the regulation of PLC-b subtypes by G proteins, 140NHERF, 142–143Par-3, 145PDZ-binding motif, 141potential PDZ domain proteins that interact with PLC-b subtypes and GPCRs, 146–147PSD-95, 145–146role of PDZ domain proteins in subtype-specific role of PLC-b in GPCR-mediated signaling, 141–142Shank2, 143–145

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Temporal order of DNA replication, reside in the epigenetic code specified by chromosomalproteins, 266–269

Thrombosis, weeble chimeric mice have propensity for, 104Transcription, and gene loops, control of eukaryotic gene expression, 118–124characteristics of, 120–121chromosome conformation capture, 120dependent upon components of promoter and terminator complexes, 121genetic suppression and discovery of, 118–119Ssu72 is an integral component of the CPF 30-end processing complex, 120Ssu72 is a Pol II CTD phosphatase, 119–120TFIIB at the terminator, 121–122

Transcriptional regulators, A-type lamins and associated proteins bind to chromatin and, 246, 249Transcription factor II B (TFIIB), role in gene loops and transcriptional memory, 119–123Tumor suppressor, PTEN is haploinsufficient for, 37–38, 40, 42, 44Tumor suppressor proteins, Nit proteins also appear to behave as, 215