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Genomes and Genes
| Harald WajantSummaryCountry: Germany Publications
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Publications
NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIPSebastian Kreuz
Institute of Cell Biology and Immunology, University of Stuttgart, Germany
J Cell Biol 166:369-80. 2004..Thus, protection against Fas-induced apoptosis in a FLIP-independent manner converted a proapoptotic Fas signal into an inflammatory NFkappaB-related response...
A CD40-CD95L fusion protein interferes with CD40L-induced prosurvival signaling and allows membrane CD40L-restricted activation of CD95Constance Assohou-Luty
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany
J Mol Med 84:785-97. 2006....
Engineering death receptor ligands for cancer therapyHarald Wajant
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Wurzburg, Germany Electronic address
Cancer Lett 332:163-74. 2013..Here, we summarize strategies how these limitations can be overcome by genetic engineering...- The role of TNF in cancerHarald Wajant
Department of Molecular Medicine, Medical Clinic and Polyclinic II, University of Wurzburg, Rontgenring 11, 97070, Wuerzburg, Germany
Results Probl Cell Differ 49:1-15. 2009.... - Therapeutic targeting of CD95 and the TRAIL death receptorsJeannette Gerspach
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
Recent Pat Anticancer Drug Discov 6:294-310. 2011.... - TNFR1-induced activation of the classical NF-κB pathwayHarald Wajant
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Germany
FEBS J 278:862-76. 2011..Here, we sum up the known details of TNFR1-induced IKK activation, address arising contradictions and discuss possible explanations resolving the apparent discrepancies... - Targeting the FLICE Inhibitory Protein (FLIP) in cancer therapyHarald Wajant
Department of Molecular Medicine Medical Polyclinic, University of Wuerzburg Roentgenring 11, 97070 Wuerzburg, Germany
Mol Interv 3:124-7. 2003..Thus, FLIP, which normally prevents inappropriate apoptosis, may become a tumor progression factor. Strategies to overcome this FLIP-mediated blockade of programmed cell death in tumors might become useful for positive prognoses... - Death receptorsHarald Wajant
Department of Molecular Internal Medicine, Medical Polyclinic, University of Wuerzburg, Roentgenring 11, 97 070 Wuerzburg, Germany
Essays Biochem 39:53-71. 2003..This review is focused on the molecular mechanisms of apoptotic and non-apoptotic death receptor signalling in light of the phenotype of mice deficient in the various death receptors... - Tumor necrosis factor receptor-associated factor (TRAF) 1 regulates CD40-induced TRAF2-mediated NF-kappaB activationMariola Fotin-Mleczek
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
J Biol Chem 279:677-85. 2004.... - Caspase-mediated cleavage converts the tumor necrosis factor (TNF) receptor-associated factor (TRAF)-1 from a selective modulator of TNF receptor signaling to a general inhibitor of NF-kappaB activationFrank Henkler
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
J Biol Chem 278:29216-30. 2003.... - Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathwayClaudia Roos
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Wurzburg, Germany
J Immunol 185:1593-605. 2010.... - Signaling active CD95 receptor molecules trigger co-translocation of inactive CD95 molecules into lipid raftsIsabell Lang
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany
J Biol Chem 287:24026-42. 2012..In sum, this shows that signaling-active CD95 molecules not only enhance their own association with the lipid raft-containing membrane fraction but also those of inactive CD95 molecules... - Oligomerized tumor necrosis factor-related apoptosis inducing ligand strongly induces cell death in myeloma cells, but also activates proinflammatory signaling pathwaysDaniela Berg
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Germany
FEBS J 276:6912-27. 2009.... - Death receptor-induced signaling pathways are differentially regulated by gamma interferon upstream of caspase 8 processingDaniela Siegmund
Department of Molecular Internal Medicine, Medical Polyclinic, University of Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany
Mol Cell Biol 25:6363-79. 2005..Overexpression of FLIP(L) and FLIP(S) inhibited Fas- as well as TRAIL-mediated NF-kappaB activation and apoptosis induction in IFN-gamma-primed cells suggesting that both responses are coregulated at the level of the DISC... - The extracellular domains of FasL and Fas are sufficient for the formation of supramolecular FasL-Fas clusters of high stabilityFrank Henkler
Department of Molecular Internal Medicine, Medical Polyclinic, University of Wuerzburg, 97070 Wuerzburg, Germany
J Cell Biol 168:1087-98. 2005.... - Non-apoptotic Fas signalingHarald Wajant
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, Germany
Cytokine Growth Factor Rev 14:53-66. 2003..This review is focused on the non-apoptotic functions of the FasL/Fas system. In particular, the similarities and differences of the molecular mechanisms of apoptotic and non-apoptotic Fas signaling are addressed... - A TNF receptor 2 selective agonist rescues human neurons from oxidative stress-induced cell deathRoman Fischer
Institute of Cell Biology and Immunology, University Stuttgart, Stuttgart, Germany
PLoS ONE 6:e27621. 2011..Since TNFR2 is not only promoting anti-apoptotic responses but also plays an important role in tissue regeneration, activation of TNFR2 signaling by TNC-scTNF(R2) appears a promising strategy to ameliorate neurodegenerative processes... - Studies of binding of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) to fibroblast growth factor inducible 14 (Fn14)Andrea Fick
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany
J Biol Chem 287:484-95. 2012..Thus, although ∼25 activated TNFR1 trimers were sufficient to trigger half-maximal IL8 production, more than 2500 cell-bound oligomerized TWEAK trimers were required to elicit a similar response... - Tumor therapeutics by design: targeting and activation of death receptorsHarald Wajant
Department of Internal Molecular Medicine, Medical Polyclinic, University of Wuerzburg, Germany
Cytokine Growth Factor Rev 16:55-76. 2005.... - Trimer stabilization, oligomerization, and antibody-mediated cell surface immobilization improve the activity of soluble trimers of CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF receptor ligandAgnes Wyzgol
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany
J Immunol 183:1851-61. 2009..Furthermore, surface immobilization might be exploited to gain locally enhanced ligand activity... - Selective inhibition of FLICE-like inhibitory protein expression with small interfering RNA oligonucleotides is sufficient to sensitize tumor cells for TRAIL-induced apoptosisDaniela Siegmund
Institute of Cell Biology and Immunology, University of Stuttgart, Germany
Mol Med 8:725-32. 2002..The combination of TRAIL and FLIP-targeting siRNA could therefore be a useful strategy to attack cancer cells, which are resistant to TRAIL alone... - Production, purification, and characterization of scFv TNF ligand fusion proteinsAndrea Fick
Division for Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Wurzburg, Germany
Methods Mol Biol 907:597-609. 2012.... - Improving TNF as a cancer therapeutic: tailor-made TNF fusion proteins with conserved antitumor activity and reduced systemic side effectsJeannette Gerspach
Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany
Biofactors 35:364-72. 2009..Here, we review the progress made toward improving the efficacy of TNF by genetic engineering, tumor targeting, and introduction of prodrug concepts... - Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2 (TNFR2)Hilka Rauert
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany
J Biol Chem 285:7394-404. 2010..Thus, we identified activation of the alternative NFkappaB pathway as a TNF signaling effect that can be specifically assigned to TNFR2 and membrane TNF... - Superior serum half life of albumin tagged TNF ligandsNicole Muller
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany
Biochem Biophys Res Commun 396:793-9. 2010..In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands... - Role of caspases in CD95L- and TRAIL-induced non-apoptotic signalling in pancreatic tumour cellsDaniela Siegmund
Department of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University of Wuerzburg, and Division of Molecular Oncology, Clinic for General Surgery and Thoracic Surgery, University Hospital Schleswig Holstein, Kiel, Germany
Cell Signal 19:1172-84. 2007..Consequently, an NFkappaB and ERK stimulating, caspase-dependent factor must operate downstream of the DISC in Colo357-BclxL cells... - Sustained JNK activation in response to tumor necrosis factor is mediated by caspases in a cell type-specific mannerAndreas Wicovsky
Department of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University of Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany
J Biol Chem 282:2174-83. 2007..Thus, sustained JNK activation by TNF has no obligate role in TNF-induced cell death and is mediated by caspases and reactive oxygen species in a cell type-specific manner... - Intracellular localization and transcriptional regulation of tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4)Heike Glauner
Institute of Cell Biology and Immunology and Institute of Industrial Genetics, University of Stuttgart, Germany Institute of Immunology, Christian Albrechts University of Kiel, Germany
Eur J Biochem 269:4819-29. 2002..These data suggest that activation of the NF-kappaB pathway is involved in up-regulation of TRAF4 in T-cells... - Endogenous membrane tumor necrosis factor (TNF) is a potent amplifier of TNF receptor 1-mediated apoptosisMonika Weingärtner
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
J Biol Chem 277:34853-9. 2002..Moreover, we give evidence that this mechanism circumvents the need of the prolonged presence of exogenous soluble TNF for TNF-R1-mediated apoptosis induction... - Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8Mariola Fotin-Mleczek
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
J Cell Sci 115:2757-70. 2002..Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level... - CD95L/FasL and TRAIL in tumour surveillance and cancer therapyHarald Wajant
Department of Molecular Internal Medicine, Medical Polyclinic, University of Wuerzburg, Roentgenring 11, 97070 Wuerzburg, Germany
Cancer Treat Res 130:141-65. 2006..This chapter focuses on the relevance of CD95L/FasL and TRAIL for the tumour surveillance function of natural killer cells and cytotoxic T-cells and discuss current concepts of utilizing these ligands in tumour therapy... - Death ligands designed to kill: development and application of targeted cancer therapeutics based on proapoptotic TNF family ligandsJeannette Gerspach
Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany
Results Probl Cell Differ 49:241-73. 2009..Preclinical data on newly derived variants and fusion proteins based on these death ligands, designed to act in a tumor restricted manner, thereby preventing a systemic, potentially harmful action, will also be discussed... - Activity of soluble OX40 ligand is enhanced by oligomerization and cell surface immobilizationNicole Muller
Department of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University of Wuerzburg, Germany
FEBS J 275:2296-304. 2008..Trimeric single chain OX40L fusion proteins therefore represent a novel type of OX40L-derived immunostimulatory molecule with potentially reduced systemic side effects... - TRAIL and NFkappaB signaling--a complex relationshipHarald Wajant
Department of Molecular Internal Medicine Medical Polyclinic, University of Wurzburg, D 97070 Wurzburg, Germany
Vitam Horm 67:101-32. 2004..Third, the TRAIL death receptors can activate the NFkappaB pathway. This chapter summarizes basic knowledge regarding the understanding of the NFkappaB pathway and focuses on its multiple roles in TRAIL signaling... - Integrin-linked kinase is dispensable for multiple myeloma cell survivalTorsten Steinbrunn
Department of Internal Medicine II, Comprehensive Cancer Center Mainfranken, University Hospital of Wurzburg, Wurzburg, Germany
Leuk Res 36:1165-71. 2012..Although this effect was largely tumor cell-specific it is unlikely to have been mediated via ILK. We conclude that ILK does not play a prominent role in the promotion or sustenance of established MM... - Interferons induce proteolytic degradation of TRAILR4Andreas Wicovsky
Department of Molecular Internal Medicine, Medical Polyclinic, , , 97070 Wurzburg, Germany
Biochem Biophys Res Commun 337:184-90. 2005..Thus, the apoptosis-inducing action of interferons may not only rely on the well-established induction of TRAIL in effector cells but also on concomitant down-regulation of its antagonizing decoy receptor TRAILR4 in target cells... - SMAC mimetic BV6 induces cell death in monocytes and maturation of monocyte-derived dendritic cellsNicole Müller-Sienerth
Department of Internal Medicine II, University Hospital Wurzburg, Wurzburg, Germany
PLoS ONE 6:e21556. 2011..In view of the overwhelming importance of the NFκB transcription factors in the immune system, we analyzed here the effects of the SMAC mimetic BV6 on immune cells... - Generation of a FasL-based proapoptotic fusion protein devoid of systemic toxicity due to cell-surface antigen-restricted ActivationDierk Samel
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
J Biol Chem 278:32077-82. 2003..The principle described here for the first time, in which cell-surface antigen-mediated activation of Fas permits local activation of Fas in vivo, opens novel avenues for the use of Fas signaling in cancer therapy... - The IKK inhibitor Bay 11-7082 induces cell death independent from inhibition of activation of NFκB transcription factorsHilka Rauert-Wunderlich
Division of Molecular Internal Medicine, Department of Internal Medicine II, University of Wurzburg, Wurzburg, Germany
PLoS ONE 8:e59292. 2013..In accordance with the latter, we further observed that concomitant knockdown of IKK1 and IKK2 did not have any major short-term adverse effect on the viability of MM cells... - Target-selective activation of a TNF prodrug by urokinase-type plasminogen activator (uPA) mediated proteolytic processing at the cell surfaceJeannette Gerspach
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, Stuttgart, 70569, Germany
Cancer Immunol Immunother 55:1590-600. 2006..Processing optimised TNF prodrugs should increase the proportion of active therapeutic within the targeted tissue and thus potentially enhance tumor response rate... - The Fas signaling pathway: more than a paradigmHarald Wajant
Institute of Cell Biology and Immunology, Allmandring 31, University of Stuttgart, 70 569 Stuttgart, Germany
Science 296:1635-6. 2002.... - Apoptosis is not required for acantholysis in pemphigus vulgarisEnno Schmidt
Department of Dermatology, University of Wurzburg, Wurzburg, Germany
Am J Physiol Cell Physiol 296:C162-72. 2009..Taken together, we conclude that apoptosis is not a prerequisite for skin blistering in PV but may occur secondary to acantholysis... - The role of FasL and Fas in health and diseaseMartin Ehrenschwender
Department of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University of Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany
Adv Exp Med Biol 647:64-93. 2009..In this chapter, we will briefly introduce essential general aspects of the FasL-Fas system before reviewing its physiological and pathophysiological relevance. Finally, FasL-Fas-related therapeutic tools and concepts will be addressed... - Structure determinants of substrate specificity of hydroxynitrile lyase from Manihot esculentaHanspeter Lauble
Institut für Organische Chemie der Universität Stuttgart, D 70569 Stuttgart, Germany
Protein Sci 11:65-71. 2002..1 A resolution shows the presence of two hydroxybenzaldehyde molecules in a sandwich type arrangement in the active site with an additional hydrogen bridge to the reacting center... - Enhanced basal AP-1 activity and de-regulation of numerous genes in T cells transgenic for a dominant interfering mutant of FADD/MORT1Svetla Chaneva
Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany
Eur J Immunol 34:3006-15. 2004..The constitutive activation of AP-1 may thus serve to precondition resting T cells for an enhanced expression of many immunologically relevant genes during activation... - CD95 and TRAF2 promote invasiveness of pancreatic cancer cellsAnna Trauzold
Molecular Oncology Unit, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany
FASEB J 19:620-2. 2005..Thus, TRAF2 overexpression does not only block apoptosis induction by CD95 but also converts this death receptor into a mediator of invasiveness... - Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasisJan Hendrik Egberts
Division of Molecular Oncology, Department of General Surgery and Thoracic Surgery, University Hospital of Schleswig Holstein, Campus Kiel, Kiel, Germany
Cancer Res 68:1443-50. 2008..Thus, tumor cell-derived TNFalpha plays a profound role in malignancy of PDAC, and inhibition of TNFalpha represents a promising therapeutic option particularly in adjuvant therapy after subtotal pancreatectomy... - The CD95 receptor: apoptosis revisitedMarcus E Peter
Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA
Cell 129:447-50. 2007..Recent evidence suggests, however, that CD95 mediates not only apoptosis but also diverse nonapoptotic functions depending on the tissue and the conditions...