Skip to main content
Article thumbnail
Location of Repository

The Identification and Characterisation of Novel Proteins and Metabolic Signalling Pathways that Regulate TRAIL-Induced Apoptosis

By Gemma Louise Robinson

Abstract

TNF-related apoptosis inducing ligand (TRAIL) is a putative anti-cancer cytokine that is relatively specific for transformed cells however Mantle Cell Lymphoma (MCL) is resistant. TRAIL induces apoptosis through formation of a Death-Inducing Signalling Complex (DISC) and the successive activation of a caspase cascade. Therefore, the aims of this thesis were two-fold: firstly to examine the known and novel protein components of the DISC through mass spectrometry analysis and second to determine how cellular metabolism, specifically glucose-deprivation, influences TRAIL-induced apoptosis. \ud A tagged variant of TRAIL was used to capture the DISC from a TRAIL-sensitive MCL-derived cell line (Z138) allowing for its purification and subsequent proteomic analysis by mass spectrometry. From this study, it was found that the transferrin receptor (TFR1) may interact with the DISC, specifically with the TRAIL-receptors, where it potentially modulates TRAIL-induced apoptosis and/or receptor-mediated endocytosis. In addition, it was observed that the known DISC component FADD was present in sub-stoichiometric amounts compared to caspase-8 and this permitted the identification of a novel DISC structure based on caspase-8 chain formation. In parallel to this, glucose-deprivation studies were performed, which showed that, in the absence of glucose, Z138 cells was less sensitive to TRAIL-induced apoptosis. Furthermore, these cells also showed a reduced sensitivity to both ABT-737 and x-ray radiation. As a result, proteomic, ultra-structural and gene profiling studies were performed on Z138 cells cultured in the absence of glucose, which demonstrated a switch towards an anti-apoptotic/pro-survival phenotype

Publisher: University of Leicester
Year: 2012
OAI identifier: oai:lra.le.ac.uk:2381/10196

Suggested articles

Citations

  1. (2002). (MRC Toxicology Unit) essentially as previously described in
  2. (2008). 2-deoxy-D-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer. Free Radic.
  3. (2009). 2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAILR2.
  4. (2006). 2-Deoxyglucose: an anticancer and antiviral therapeutic, but not any more a low glucose mimetic.
  5. (1997). A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis.
  6. (2001). A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins.
  7. (1992). A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.
  8. (2008). A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death.
  9. (1998). A phylogenetic approach to the identification of phosphoglucomutase genes.
  10. (2005). A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid.
  11. (2010). A systematic approach to protein glycosylation analysis: a path through the maze.
  12. (1997). Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway.
  13. (2006). Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis.
  14. (2002). Activation of the p53 tumor suppressor protein.
  15. (2005). Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicinand bortezomib-induced cell death.
  16. (2007). Agm1/Pgm3-mediated sugar nucleotide synthesis is essential for hematopoiesis and development.
  17. (2002). Akt enhances Mdm2-mediated ubiquitination and degradation of p53.
  18. (2004). Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases.
  19. (2002). Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake.
  20. (2007). AKT/PKB signaling: navigating downstream.
  21. (2005). AMP-activated protein kinase induces a p53-dependent metabolic checkpoint.
  22. (2005). An inhibitor of Bcl-2 family proteins induces regression of solid tumours.
  23. (2008). An integrated genomic analysis of human glioblastoma multiforme.
  24. (2000). and are essential for apoptosis mediated by TRAIL receptor 2.
  25. (1996). Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-kappa
  26. (2002). Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments.
  27. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
  28. (2008). Apoptosis: controlled demolition at the cellular level.
  29. (2005). Apoptosis. p53 and PUMA: a deadly duo.
  30. (1999). Apoptosis. Searching for FLASH domains.
  31. (2007). Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration.
  32. (1961). Astudy of the citric acid cycle in certain tumour tissue.
  33. (2006). Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance.
  34. (2003). BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis.
  35. (1998). BCL-2 family: regulators of cell death.
  36. (1988). Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells.
  37. (1996). Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice.
  38. (2011). BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane.
  39. (1999). Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis.
  40. (1998). Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors.
  41. (2008). Biochemical analysis of the native TRAIL deathinducing signaling complex.
  42. (2008). Brick by brick: metabolism and tumor cell growth.
  43. (2002). c-FLIP(L) is a dual function regulator for caspase8 activation and CD95-mediated apoptosis.
  44. (2003). c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade.
  45. (2010). Cancer-associated IDH mutations: biomarker and therapeutic opportunities.
  46. (2009). Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.
  47. (1998). Cap-independent polysomal association of natural mRNAs encoding c-myc, BiP, and eIF4G conferred by internal ribosome entry sites.
  48. (2008). Cardiolipin provides an essential activating platform for caspase-8 on mitochondria.
  49. (2007). Cardiolipin: setting the beat of apoptosis.
  50. (2002). Caspase-10 is recruited to and activated at the native TRAIL and CD95 deathinducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8.
  51. (2006). Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis.
  52. (2010). Caspase-7: a protease involved in apoptosis and inflammation.
  53. (2003). Caspase-activation pathways in apoptosis and immunity.
  54. (1997). Caspases: the executioners of apoptosis.
  55. (1996). CD95 (APO-1/Fas)-associating signalling proteins.
  56. (2008). CD95 stimulation results in the formation of a novel death effector domain protein-containing complex.
  57. (2004). Cell death: critical control points.
  58. (2005). Cells die with increased cytosolic ATP during apoptosis: a bioluminescence study with intracellular luciferase.
  59. (2001). Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex.
  60. (2003). Cellular FLICE-inhibitory protein: an attractive therapeutic target?
  61. (2003). Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy.
  62. (2002). Characterization of the in vivo function of TNF-alpha-related apoptosis-inducing ligand, TRAIL/Apo2L, using TRAIL/Apo2L gene-deficient mice.
  63. (1998). Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis.
  64. (2003). Cloning and characterization of a novel gene PDRG that is differentially regulated by p53 and ultraviolet radiation.
  65. (1984). Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation.
  66. (1998). Cluster analysis and display of genome-wide expression patterns.
  67. (2002). Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development.
  68. (2001). Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding.
  69. (2009). Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling.
  70. (2010). Current treatment strategy and new agents in mantle cell lymphoma.
  71. (1995). Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor.
  72. (1997). Daxx, a novel Fasbinding protein that activates JNK and apoptosis.
  73. (2001). Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8.
  74. (1998). Death receptors: signaling and modulation.
  75. (2007). Death-receptor Oglycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL.
  76. (2006). Developmental apoptosis in C. elegans: a complex CEDnario.
  77. (2001). Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions.
  78. (1999). Differential modulation of apoptosis sensitivity in CD95 type I and type II cells.
  79. (2001). Dimer formation drives the activation of the cell death protease caspase 9.
  80. (2008). Directing cancer cells to self-destruct with pro-apoptotic receptor agonists.
  81. (1997). Discovery and analysis of inflammatory disease-related genes using cDNA microarrays.
  82. (1999). Distinct caspase cascades are initiated in receptor-mediated and chemicalinduced apoptosis.
  83. (2010). Distinct death mechanisms in Drosophila development.
  84. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.
  85. (2004). DNA damage-induced apoptosis.
  86. (2001). DNA hybridization arrays: a powerful technology for nutritional and obesity research.
  87. (1976). Dna in chromatin of irradiated lymphoid tissues degrades in vivo into regular fragments.
  88. (1999). DNA microarrays in drug discovery and development.
  89. (2010). Doxorubicin in vivo rapidly alters expression and translation of myocardial electron transport chain genes, leads to ATP loss and caspase 3 activation.
  90. (1985). Effects of 2-deoxy-D-glucose on glycolysis, proliferation kinetics and radiation response of human cancer cells.
  91. (1990). Effects of 2-deoxyglucose on drug-sensitive and drug-resistant human breast cancer cells: toxicity and magnetic resonance spectroscopy studies of metabolism.
  92. (2006). Effects of transferrin receptor blockade on cancer cell proliferation and hypoxia-inducible factor function and their differential regulation by ascorbate.
  93. (2007). Enhanced expression of asparagine synthetase under glucose-deprived conditions protects pancreatic cancer cells from apoptosis induced by glucose deprivation and cisplatin.
  94. (1988). Enhancement of glycogen concentrations in primary cultures of rat hepatocytes exposed to glucose and fructose.
  95. (1992). Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
  96. (2000). Fas ligandinduced c-Jun kinase activation in lymphoid cells requires extensive receptor aggregation but is independent of DAXX, and Fas-mediated cell death does not involve
  97. (2003). Fasassociated factor 1, FAF1, is a member of Fas death-inducing signaling complex.
  98. (2008). Fight against cancer - strategies that prevent, cure and care.
  99. (1997). FLICE is activated by association with the CD95 deathinducing signaling complex (DISC).
  100. (1997). FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b.
  101. (1996). FLICE, a novel FADDhomologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.
  102. (2009). Following TRAIL's path in the immune system.
  103. (2011). Functions and regulation of the 70kDa ribosomal S6 kinases.
  104. (2004). Gene expression profiling identifies clinically relevant subtypes of prostate cancer.
  105. (1988). Genes specifically expressed at growth arrest of mammalian cells.
  106. (2007). Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics.
  107. (1986). Genetic control of programmed cell death in the nematode C.
  108. (2006). Genetic testing in pheochromocytoma- and paraganglioma-associated syndromes.
  109. (2007). Genome-wide analysis of mRNA polysomal profiles with spotted DNA microarrays.
  110. (2006). Genomic alterations in human malignant glioma cells associate with the cell resistance to the combination treatment with tumor necrosis factor-related apoptosis-inducing ligand and chemotherapy.
  111. (2000). Genomics, gene expression and DNA arrays.
  112. (2011). Global cancer statistics.
  113. (2001). Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase.
  114. (2010). Glucose deprivation induces an atypical form of apoptosis mediated by caspase-8 in Bax-, Bak-deficient cells.
  115. (2006). Glucose metabolism and cancer.
  116. (2002). Glucose transporters: expression, regulation and cancer.
  117. (2007). Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator.
  118. (2008). Glucoseregulated protein 75 suppresses apoptosis induced by glucose deprivation in PC12 cells through inhibition of Bax conformational change.
  119. (2009). Glycogen synthase kinase 3: more than a namesake.
  120. (2006). Glycolysis inhibition for anticancer treatment.
  121. (2010). Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation.
  122. (2005). Glycolytic enzymes can modulate cellular life span.
  123. (2009). Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect" and a pivotal target for effective therapy.
  124. (2004). Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax
  125. (2007). HIF-1-regulated glucose metabolism: a key to apoptosis resistance?
  126. (2010). HIF-1: upstream and downstream of cancer metabolism.
  127. (2007). How apoptosis got the immune system in shape.
  128. (2009). Human caspases: activation, specificity, and regulation.
  129. (1994). Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria.
  130. (1996). Human ICE/CED-3 protease nomenclature.
  131. (2010). Human pyruvate kinase M2: a multifunctional protein.
  132. (2010). HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.
  133. (1996). I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction.
  134. (1999). IAP family proteins--suppressors of apoptosis.
  135. (2010). IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer.
  136. (1995). Identification and characterization of a new member of the TNF family that induces apoptosis.
  137. (1996). Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32.
  138. (1999). Identification and characterization of genes associated with human hepatocellular carcinogenesis.
  139. (1995). Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis.
  140. (1997). Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL.
  141. (2000). Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques.
  142. (2002). Identification of human phosphoglucomutase 3 (PGM3) as N-acetylglucosamine-phosphate mutase (AGM1).
  143. (2002). Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice.
  144. (1996). Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family.
  145. (2000). Induction of apoptosis by cancer chemotherapy.
  146. (2008). Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance.
  147. (2003). Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.
  148. (1993). Inhibition of doxorubicin-induced apoptosis in vivo by 2-deoxy-D-glucose. Cancer Res.
  149. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase.
  150. (1987). Inhibition of established rat fibrosarcoma growth by the glucose antagonist 2-deoxy-D-glucose.
  151. (2011). Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells.
  152. (2003). Inhibition of glucose metabolism sensitizes tumor cells to death receptor-triggered apoptosis through enhancement of death-inducing signaling complex formation and apical procaspase-8 processing.
  153. (2010). Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression.
  154. (1994). Interactive regulation of the pyruvate dehydrogenase complex and the carnitine palmitoyltransferase system.
  155. (1997). Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis.
  156. (2007). Investigating the interaction between osteoprotegerin and receptor activator of NF-kappaB or tumor necrosis factor-related apoptosis-inducing ligand: evidence for a pivotal role for osteoprotegerin in regulating two distinct pathways.
  157. (2003). Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function.
  158. Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria.
  159. (2004). Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction.
  160. (2007). Lipid rafts and nonrafts mediate tumor necrosis factor related apoptosisinducing ligand induced apoptotic and nonapoptotic signals in non small cell lung carcinoma cells.
  161. (2000). Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.
  162. (2002). Low glucose-enhanced TRAIL cytotoxicity is mediated through the ceramide-Akt-FLIP pathway.
  163. (2011). Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era.
  164. (2011). Mantle cell lymphoma: report of the 2010 mantle cell lymphoma consortium workshop.
  165. (2010). Mantle cell lymphoma: The promise of new treatment options.
  166. (2007). MAPK kinase kinase regulation of SAPK/JNK pathway. Topics in Current Genetics 20, Stennicke,
  167. (1991). Mechanisms and functions of cell death.
  168. (2005). Mechanisms of apoptosis through structural biology.
  169. (2005). Mechanisms of resistance to TRAIL-induced apoptosis in cancer.
  170. (2002). Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell chronic lymphocytic leukaemia.
  171. (2002). MEK kinase 1 induces mitochondrial permeability transition leading to apoptosis independent of cytochrome c release.
  172. (2009). Metabolic transformation in cancer.
  173. (2006). Method for monitoring of mitochondrial cytochrome c release during cell death: Immunodetection of cytochrome c by flow cytometry after selective permeabilization of the plasma membrane.
  174. (2008). Methyl jasmonate binds to and detaches mitochondria-bound hexokinase.
  175. (2002). Missing pieces in the NF-kappaB puzzle.
  176. (2008). Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia.
  177. (2002). Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis.
  178. (2002). Mitochondrial bound type II hexokinase: a key player in the growth and survival of many cancers and an ideal prospect for therapeutic intervention.
  179. (2010). Mitochondrial control of caspasedependent and -independent cell death. Cell Mol. Life Sci.
  180. (1999). Mitochondrial depolarization accompanies cytochrome c release during apoptosis in PC6 cells.
  181. (2003). Mitochondrial membrane potential regulates matrix configuration and cytochrome c release during apoptosis.
  182. (1993). Mitotic repression of transcription in vitro.
  183. (2005). Mobilization of vacuolar iron by AtNRAMP3 and AtNRAMP4 is essential for seed germination on low iron.
  184. (2001). Modulation of tumor necrosis factor apoptosis-inducing ligand- induced NF-kappa B activation by inhibition of apical caspases.
  185. (2005). Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer.
  186. (1999). Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor.
  187. (1992). Molecular cloning of the interleukin-1 beta converting enzyme.
  188. (2005). Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand.
  189. (1997). Molecular evolutionary analysis of the thiamine-diphosphate-dependent enzyme,
  190. (2008). Molecular genetic characterization reveals new subsets of mantle cell lymphoma.
  191. (2002). Molecular imaging of cancer with positron emission tomography.
  192. (2004). Molecular mechanisms of caspase regulation during apoptosis.
  193. (2010). Molecular modeling of BAD complex resided in a mitochondrion integrating glycolysis and apoptosis.
  194. (2002). Molecular ordering of the initial signaling events of CD95.
  195. (2002). Morphological and biochemical aspects of apoptosis, oncosis and necrosis.
  196. (2007). Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells.
  197. (2002). Multiwell in-gel protein digestion and microscale sample preparation for protein identification by mass spectrometry.
  198. (1999). mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II.
  199. (2010). New insights into apoptosis signaling by Apo2L/TRAIL.
  200. (1999). NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase.
  201. NF-kappaB addiction and its role in cancer: 'one size does not fit all'.
  202. (2002). NF-kappaB in cancer: from innocent bystander to major culprit.
  203. (2011). NFkB controls energy homestasis and metabolic adaptation by upregulating mitochondrial respiration.
  204. (1998). not caspase-2, in the induction of apoptosis in Bchronic lymphocytic leukemia cells.
  205. (2000). Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.
  206. (2006). Nuclear factor-kappaB in cancer development and progression.
  207. (1999). Nutrient and hormonal regulation of pyruvate kinase gene expression.
  208. (2008). Oglycosylation of FoxO1 increases its transcriptional activity towards the glucose 6-phosphatase gene.
  209. (1956). On the origin of cancer cells.
  210. (2005). Oncogenic alterations of metabolism and the warburg effect.
  211. (1999). Oncogenic alterations of metabolism.
  212. (2009). Optimal and consistent protein glycosylation in mammalian cell culture.
  213. (1998). Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL.
  214. (2004). Overexpression of MEKK3 confers resistance to apoptosis through activation of NFkappaB.
  215. (2006). P53 Regulates Mitochondrial Respiration.
  216. (2007). P53: New Roles in Metabolism.
  217. (2005). p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway.
  218. Parallel human genome analysis: microarray-based expression monitoring of 1000 genes.
  219. (2006). Pathways from glutamine to apoptosis.
  220. (2011). PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress.
  221. (2005). Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements.
  222. (1988). PET in clinical oncology.
  223. (1996). Phosphatidylserine externalization during CD95-induced apoptosis of cells and cytoplasts requires ICE/CED-3 protease activity.
  224. (2002). Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency.
  225. (2008). Polymorphisms in mitochondrial genes and prostate cancer risk. Cancer Epidemiol. Biomarkers Prev.
  226. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans.
  227. (1994). Prevention of vertebrate neuronal death by the crmA gene.
  228. (2004). Pro-apoptotic proteins released from the mitochondria regulate the protein composition and caspase-processing activity of the native Apaf1/caspase-9 apoptosome complex.
  229. (2001). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.
  230. (1998). Properties and functions of the thiamin diphosphate dependent enzyme transketolase.
  231. (2002). Protein phosphatase 1--targeted in many directions.
  232. (2003). Puma is an essential mediator of p53-dependent and -independent apoptotic pathways.
  233. (2001). PUMA, a novel proapoptotic gene, is induced by p53.
  234. (2008). Pyruvate kinase M2 is a phosphotyrosine-binding protein.
  235. (1988). Pyruvate kinase type M2 is phosphorylated at tyrosine residues in cells transformed by Rous sarcoma virus.
  236. (1995). Quantitative monitoring of gene expression patterns with a complementary DNA microarray.
  237. (2006). Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors.
  238. (2007). Receptor-mediated endocytosis is not required for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
  239. (2008). Recombinant TRAIL and TRAIL receptor analysis.
  240. (2009). Reconstitution of the death-inducing signaling complex reveals a substrate switch that determines CD95-mediated death or survival.
  241. (2011). Regulation of cancer cell metabolism.
  242. (1982). Regulation of cellular energy metabolism.
  243. (2011). Regulation of cellular iron metabolism.
  244. (2003). Regulative capacity of glutamine.
  245. (1999). Reproducibility of metabolic measurements in malignant tumors using FDG PET.
  246. (2000). Requirement of JNK for stressinduced activation of the cytochrome c-mediated death pathway.
  247. (1997). Resistance of cultured peripheral T cells towards activationinduced cell death involves a lack of recruitment of FLICE (MACH/caspase 8) to the CD95 death-inducing signaling complex.
  248. (1995). Role of IRS-2 in insulin and cytokine signalling.
  249. (1999). Safety and antitumor activity of recombinant soluble Apo2 ligand.
  250. (2007). Selective inhibition of IkappaB kinase sensitizes mantle cell lymphoma B cells to TRAIL by decreasing cellular FLIP level.
  251. (2006). Sensitivity and resistance of human cancer cells to TRAIL: mechanisms and therapeutical perspectives.
  252. (1998). Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development.
  253. (2011). Signal transduction: How cells sense energy.
  254. (2004). Signaling the unfolded protein response from the endoplasmic reticulum.
  255. (2008). Silencing Bcl-2 in models of mantle cell lymphoma is associated with decreases in cyclin D1, nuclear factorkappaB, p53, bax, and p27 levels.
  256. (2006). Statistical analysis of membrane proteome expression changes in Saccharomyces cerevisiae.
  257. (2000). Steering anti-cancer drugs away from the TRAIL.
  258. (2011). Stoichiometry of the TRAIL Death-Inducing Signalling Complex: Structural modelling and in vitro reconstitution reveal a new DISC model based on capase-8 chain formation. Under Review Molecular Cell Drakas,
  259. (2001). Structural basis for the activation of human procaspase-7.
  260. (1994). Structure and mechanism of interleukin-1 beta converting enzyme.
  261. (1997). Substrate specificities of caspase family proteases.
  262. (2011). Sugar-free approaches to cancer cell killing.
  263. (2000). Surfing the p53 network.
  264. (1962). Synthesis of RNA and protein during mitosis in mammalian tissue culture cells.
  265. T2BP, a novel TRAF2 binding protein, can activate NF-kappaB and AP-1 without TNF stimulation.
  266. (2002). Targeting death and decoy receptors of the tumour-necrosis factor superfamily.
  267. (2011). Targeting hypoxia in cancer therapy.
  268. (2009). Targeting the phosphoinositide 3-kinase pathway in cancer.
  269. (2008). Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations.
  270. (2002). The Apaf-1 apoptosome: a large caspase-activating complex.
  271. (1997). The apoptotic cysteine protease CPP32.
  272. (2004). The C-terminal tails of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas receptors have opposing functions in Fas-associated death domain (FADD) recruitment and can regulate agonist-specific mechanisms of receptor activation.
  273. (1993). The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 betaconverting enzyme.
  274. (1998). The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9.
  275. (1999). The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis.
  276. (1983). The embryonic cell lineage of the nematode Caenorhabditis elegans.
  277. (2001). The essential role of MEKK3 in TNF-induced NF-kappaB activation.
  278. (2002). The genetic basis of human cancer (USA: The McGraw-Hill Companies).
  279. (1999). The genetics of cancer--a 3D model.
  280. (2000). The hallmarks of cancer.
  281. (2011). The human DEK oncogene stimulates beta-catenin signaling, invasion and mammosphere formation in breast cancer.
  282. (1963). The interaction of poliovirus RNA with Escherichia coli ribosomes.
  283. (2007). The JNK signal transduction pathway.
  284. (2008). The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth.
  285. (2011). The metabolic advantage of tumor cells.
  286. (2011). The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis.
  287. (2000). The oligomycin axis of mitochondrial ATP synthase: OSCP and the proton channel.
  288. (2002). The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
  289. (2007). The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.
  290. (1979). The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans.
  291. (2004). The protein structures that shape caspase activity, specificity, activation and inhibition.
  292. (1997). The receptor for the cytotoxic ligand TRAIL.
  293. (1985). The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells.
  294. (1990). The role of transferrin in the mechanism of cellular iron uptake.
  295. (2002). The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif.
  296. (2001). The TNF and TNF receptor superfamilies: integrating mammalian biology.
  297. (1996). The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex.
  298. (2006). TIGAR, a p53-inducible regulator of glycolysis and apoptosis.
  299. (1996). TNFdependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex.
  300. (1999). To die or not to die--the quest of the TRAIL receptors.
  301. (1996). TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways.
  302. (2009). TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges.
  303. (2003). TRAIL and apoptosis induction by TNF-family death receptors.
  304. (2004). TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice.
  305. (2005). TRAIL receptor-selective mutants signal to apoptosis via TRAIL-R1 in primary lymphoid malignancies.
  306. (2007). TRAIL signalling: decisions between life and death.
  307. (2002). TRAIL-induced apoptosis is independent of the mitochondrial apoptosis mediator DAP3.
  308. (2003). TRAIL-induced signalling and apoptosis.
  309. (2010). TRAIL/TRAIL-R in hematologic malignancies.
  310. (2010). TRAILinduced apoptosis is preferentially mediated via TRAIL receptor 1 in pancreatic carcinoma cells and profoundly enhanced by XIAP inhibitors.
  311. (2010). transduction pathway to control gene expression, cell survival and differentiation.
  312. (1983). Transferrin receptors in human tissues: their distribution and possible clinical relevance.
  313. (2004). Translational profiling: the genome-wide measure of the nascent proteome. Brief Funct.
  314. (2010). Translational regulation of gene expression during conditions of cell stress.
  315. (2009). Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes.
  316. (1997). TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL.
  317. (2000). Tumor angiogenesis. Gene expression patterns identified.
  318. (2010). Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation.
  319. (2009). Tumor suppressors and cell metabolism: a recipe for cancer growth.
  320. (1999). Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo.
  321. (1998). Two CD95 (APO-1/Fas) signaling pathways.
  322. (2005). Type I and type II reactions in TRAIL-induced apoptosis -- results from doseresponse studies.
  323. (2009). Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth.
  324. (2008). Ultrastructure of the mitochondrion and its bearing on function and bioenergetics.
  325. (2007). Under normoxia, 2-deoxy-Dglucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation.
  326. (1996). Use of a cDNA microarray to analyse gene expression patterns in human cancer.
  327. (2005). Validating sequence assignments for peptide fragmentation patterns: A primer in ms/ms sequence identification.
  328. (1999). vitro: implications for microfilament reorganization during apoptosis.
  329. (2005). What have animal models taught us about the p53 pathway?
  330. (2004). Why do cancers have high aerobic glycolysis?
  331. (1998). Z-138: a new mature B-cell acute lymphoblastic leukemia cell line from a patient with transformed chronic lymphocytic leukemia.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.