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Genomes and Genes | Ulf R RappSummaryCountry: Germany Publications
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Publications
Oncogene-induced plasticity and cancer stem cellsUlf R Rapp
Institute für Medizinische Strahlenkunde und Zellforschung MSZ, Bayerisches Krebsforschungszentrum, Julius Maximilians University, Wurzburg, Germany
Cell Cycle 7:45-51. 2008..In this perspective article we will summarize the experimental evidence that illustrates our concept and discuss its implications for tumor formation and tumor therapy...
Polycomb group protein Bmi1 negatively regulates IL-10 expression in activated macrophagesArnold R Sienerth
Institut fur Medizinische Strahlenkunde und Zellforschung, Wurzburg, Germany
Immunol Cell Biol 89:812-6. 2011..Our results identify Bmi1 as a repressor of IL-10 expression during macrophage activation...
Tumor induction by activated JNK occurs through deregulation of cellular growthUlrike Rennefahrt
, , , Germany
Cancer Lett 215:113-24. 2004..In vitro studies and analysis of tumor material support the conclusion that oncogenic JNK primarily transforms through its effects on cell proliferation and tumor vascularization but does not affect cell survival...
Disruption of tumor cell adhesion promotes angiogenic switch and progression to micrometastasis in RAF-driven murine lung cancerFatih Ceteci
Institut fur Medizinische Strahlenkunde und Zellforschung, Universitat Wurzburg, Versbacher Strasse 5, 97078, Wurzburg, Germany
Cancer Cell 12:145-59. 2007..In vivo, lung tumor cells with disrupted E-cadherin expressed beta-catenin target genes normally found in other endodermal lineages suggesting that reprogramming may be involved in metastatic progression...
Phospho-ERK staining is a poor indicator of the mutational status of BRAF and NRAS in human melanomaRoland Houben
Klinik fur Dermatologie, Venerologie und Allergologie, Julius Maximilians Universitat, Wurzburg, Germany
J Invest Dermatol 128:2003-12. 2008..Our findings suggest that mitogen-activated protein kinase (MAPK) activity is subject to regulation even in BRAF/NRAS mutant melanoma cells and that high MAPK pathway signaling may be important only in distinct subsets of tumor cells...
Single substitution within the RKTR motif impairs kinase activity but promotes dimerization of RAF kinaseAngela Baljuls
Theodor Boveri Institute of Bioscience, Department of Microbiology, University of Wuerzburg, Wuerzburg, Germany
J Biol Chem 286:16491-503. 2011..In summary, we provide evidence that each of the basic residues within the RKTR motif is indispensable for correct RAF function...
BuCy RAFs drive cells into MEK addictionUlf R Rapp
Institut fur Medizinische Strahlenkunde und Zellforschung, Versbacher Strasse 5, 97078 Wurzburg, Germany
Cancer Cell 9:9-12. 2006....
Bcl-2 proteins: master switches at the intersection of death signaling and the survival control by Raf kinasesUlf R Rapp
Institut für Medizinische Strahlenkunde und Zellforschung MSZ, Universitat Wurzburg, Versbacher Str 5, 97078 Wurzburg, Germany
Biochim Biophys Acta 1644:149-58. 2004..Within the scope of this review, we will discuss the contribution of Bcl-2-dependent signaling pathways to cell survival by Raf kinases and also address the underlying mechanisms...
Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo: CI-1040 strongly reduces growth and improves lung structureBoris W Kramer
Universitäts Kinderklinik Würzburg, D 97080 Wurzburg, Germany
BMC Cancer 4:24. 2004..In this study the effect of the Raf kinase inhibitor BAY 43-9006 and of the MEK inhibitor CI-1040 (PD184352) on a Raf dependent lung tumor mouse model was analyzed in detail...
Use of a recombinant Salmonella enterica serovar Typhimurium strain expressing C-Raf for protection against C-Raf induced lung adenoma in miceIvaylo Gentschev
Institut für Medizinische Strahlenkunde und Zellforschung MSZ, University of Wuerzburg, D 97078 Wuerzburg, Germany
BMC Cancer 5:15. 2005..In this study we analyzed the functionality of a new live C-Raf vaccine based on an attenuated Salmonella enterica serovar Typhimurium aroA strain in two Raf dependent lung tumor mouse models...
Use of the alpha-hemolysin secretion system of Escherichia coli for antigen delivery in the Salmonella typhi Ty21a vaccine strainIvaylo Gentschev
Institut fur Medizinische Strahlenkunde und Zellforschung, University of Wurzburg, Versbacher Str 5, D 97078 Wurzburg, Germany
Int J Med Microbiol 294:363-71. 2004..Therefore, the combination of the hemolysin secretion system and S. typhi Ty21a could form the basis for a new generation of live bacterial vaccines...
BAG-1 haplo-insufficiency impairs lung tumorigenesisRudolf Götz
Institut fur Medizinische Strahlenkunde und Zellforschung, Universitat Wurzburg, Germany
BMC Cancer 4:85. 2004....
Ras signaling: PP2A puts Ksr and Raf in the right placeThomas Raabe
, , Versbacherstr.5, , Germany
Curr Biol 13:R635-7. 2003
Raf kinases in lung tumor developmentUlf R Rapp
, Strahlenkunde und Zellforschung (MSZ, , , Versbacher-Strasse 5, D-97078, , Germany
Adv Enzyme Regul 43:183-95. 2003
BAD contributes to RAF-mediated proliferation and cooperates with B-RAF-V600E in cancer signalingLisa Polzien
Department of Microbiology, Biocenter, University of Wurzburg, 97074 Wurzburg, Germany
J Biol Chem 286:17934-44. 2011..Collectively, our findings provide new insights into the regulation of BAD function by phosphorylation and its role in cancer signaling...
Improvement of the live vaccine strain Salmonella enterica serovar Typhi Ty21a for antigen delivery via the hemolysin secretion system of Escherichia coliChristian Hotz
Institut fur Medizinische Strahlenkunde und Zellforschung, University of Wurzburg, Wurzburg, Germany
Int J Med Microbiol 299:109-19. 2009..typhi strain secreting HlyA compared with the same strain without rfaH plasmid...
B-Raf specific antibody responses in melanoma patientsJoachim Fensterle
Institut für Medizinische Strahlenkunde und Zellforschung MSZ, University Clinics of Würzburg, Versbacher Str 5, 97078 Wurzburg, Germany
BMC Cancer 4:62. 2004....
KSR--a regulator and scaffold protein of the MAPK pathwayThomas Raabe
University of W rzburg, Institut fuer Medizinische Strahlenkunde und Zellforschung MSZ, Versbacherstrasse 5, 97078 W rzburg, Germany
Sci STKE 2002:pe28. 2002..They focus on the adaptor kinase suppressor of Ras (KSR) and describe how the interactions between KSR and other proteins and the subcellular localization of KSR are regulated by phosphorylation...
BAD association with membranes is regulated by Raf kinases and association with 14-3-3 proteinsUlf R Rapp
, Versbacher Str. 5, , Germany
Adv Enzyme Regul 47:281-5. 2007
Isoform-specific interaction of C-RAF with mitochondriaAntoine Galmiche
Institut fur Medizinische Strahlenkunde und Zellforschung, University of Wurzburg, Wurzburg, Germany
J Biol Chem 283:14857-66. 2008....
Pore-forming activity of BAD is regulated by specific phosphorylation and structural transitions of the C-terminal partLisa Polzien
Theodor Boveri Institute, Department of Microbiology, University of Wuerzburg, 97074 Wuerzburg, Germany
Biochim Biophys Acta 1810:162-9. 2011..Since the functional role of the BAD C-terminal part has not been considered so far, we have investigated here the interplay of the structure and function of this region...
Regulation of RAF activity by 14-3-3 proteins: RAF kinases associate functionally with both homo- and heterodimeric forms of 14-3-3 proteinsAndreas Fischer
Bayerisches Krebsforschungszentrum, University of Wuerzburg, Wuerzburg, Germany
J Biol Chem 284:3183-94. 2009..Together, our results shed more light on the complex mechanism of RAF activation, particularly with respect to activation steps that are mediated by 14-3-3 proteins and prohibitin...
Raf kinases: oncogenesis and drug discoveryRalf Schreck
, MSZ, , , Germany
Int J Cancer 119:2261-71. 2006....
MYC-induced epigenetic activation of GATA4 in lung adenocarcinomaInês C Castro
Biocenter, Department of Microbiology, University of Wurzburg, Wurzburg, Germany
Mol Cancer Res 11:161-72. 2013..Our results thus identify a novel epigenetic mechanism by which MYC activates GATA4 leading to metastasis in lung adenocarcinoma, suggesting novel potential targets for the development of antimetastatic therapy...
Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancerMatthias Becker
Bayerisches Krebsforschungszentrum, University of Wuerzburg, Wuerzburg, Germany
PLoS ONE 4:e4230. 2009..We have previously described a RAF oncogene driven transgenic mouse model for non small cell lung cancer (NSCLC). Here we examine whether tumor initiation and growth requires the stem cell self-renewal factor Bmi1...
Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regressionKatharina Galmbacher
Institut fur Medizinische Strahlenkunde und Zellforschung, Universitat Wurzburg, Wurzburg, Germany
PLoS ONE 5:e9572. 2010..TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools...
A-RAF kinase functions in ARF6 regulated endocytic membrane trafficElena Nekhoroshkova
Institut fur Medizinische Strahlenkunde und Zellforschung, University of Wurzburg, Wurzburg, Germany
PLoS ONE 4:e4647. 2009..RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation...
Growth of transgenic RAF-induced lung adenomas is increased in mice with a disrupted PPARbeta/delta geneSabine Müller-Brüsselbach
Institute of Molecular Biology and Tumor Research IMT, Philipps University, Marburg, Germany
Int J Oncol 31:607-11. 2007..These results are relevant with respect to the clinical application of drugs modulating the activity of PPARbeta or PPARgamma...
Loss of p53 in craf-induced transgenic lung adenoma leads to tumor acceleration and phenotypic switchLev M Fedorov
Institut für Medizinische Strahlenkunde und Zellforschung MSZ, Bayerische Julius Maximilians Universität, D 97078 Wurzburg, Germany
Cancer Res 63:2268-77. 2003..This mouse model for pulmonary adenoma and adenocarcinoma should be very helpful for a better understanding of pathogenesis and treatment of this most deadly human cancer...
Thrombopoietin inhibits nerve growth factor-induced neuronal differentiation and ERK signallingAnatoly Samoylenko
University of Wurzburg, Section of Experimental Neurosurgery, Department of Neurosurgery, Josef Schneider St 11, 97080 Wurzburg, Germany
Cell Signal 20:154-62. 2008..Our data indicate that TPO via activation of its receptor-bound JAK2 delays the NGF-dependent acquisition of neuronal phenotype and decreases neuronal survival by suppressing NGF-induced ERK activity...
C-Raf controlled pathways in the protection of tumor cells from apoptosisEmily P Slater
Institute of Molecular Biology and Tumor Research (IMT) Philipps-University, Emil-Mannkopff-Strasse 2, 35033 Marburg, Germany
Int J Cancer 104:425-32. 2003....
Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRafLev M Fedorov
Institut fur Medizinische Strahlenkunde und Zellforschung, Bayerische Julius Maximilians Universität, D 97078 Wurzburg, Germany
Cancer Res 62:6297-303. 2002..These findings suggest that bcl-2 is a major susceptibility gene for development of lung cancer in mice and perhaps in humans...
Regulation of glycolysis by Raf protein serine/threonine kinasesVéronique Le Mellay
Institut für Medizinische, Strahlenkunde und Zellforschung MSZ, Universitat Wurzburg, Versbacher Str 5, Germany
Adv Enzyme Regul 42:317-32. 2002
Positive regulation of A-RAF by phosphorylation of isoform-specific hinge segment and identification of novel phosphorylation sitesAngela Baljuls
Institute for Medical Radiation and Cell Research, University of Wuerzburg, 97078 Wuerzburg, Germany
J Biol Chem 283:27239-54. 2008..Together, we provide here for the first time a detailed analysis of in vivo A-RAF phosphorylation status and demonstrate that regulation of A-RAF by phosphorylation exhibits unique features compared with B- and C-RAF...
Constitutive JNK activation in NIH 3T3 fibroblasts induces a partially transformed phenotypeUlrike E E Rennefahrt
, , , Germany
J Biol Chem 277:29510-8. 2002..Our data suggest that constitutive JNK activation elicits major aspects of cellular transformation but is unable to induce the complete set of changes which are required to establish the fully transformed phenotype...
Phospholipase D overcomes cell cycle arrest induced by high-intensity Raf signalingTroy Joseph
Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10021, USA
Oncogene 21:3651-8. 2002..These data indicate that PLD signaling provides a novel survival signal that overcomes cell cycle arrest induced by high intensity Raf signaling...
Negative regulation of mitochondrial VDAC channels by C-Raf kinaseVéronique Le Mellay
Institut für Medizinische Strahlenkunde und Zellforschung MSZ, Universitat Wurzburg, 97078 Wurzburg, Germany
BMC Cell Biol 3:14. 2002..However, apoptosis suppression by C-Raf also occurs in cells lacking expression of Bad or Bcl-2...
Hypoxia/reoxygenation induction of monocyte chemoattractant protein-1 in melanoma cells: involvement of nuclear factor-kappaB, stimulatory protein-1 transcription factors and mitogen-activated protein kinase pathwaysManfred Kunz
Department of Dermatology, University of Rostock, Augustenstr 80 84, 18055 Rostock, Germany
Biochem J 366:299-306. 2002..Functionally, H/R-induced MCP-1 production may contribute to tumour progression by committing selective pressure on tumour cells via chemoattraction and activation of tumour-infiltrating monocytes/macrophages...
Associations of B- and C-Raf with cholesterol, phosphatidylserine, and lipid second messengers: preferential binding of Raf to artificial lipid raftsMirko Hekman
Institut fuer Medizinische Strahlenkunde und Zellforschung (MSZ, University of Wuerzburg, 97078 Wuerzburg, Germany
J Biol Chem 277:24090-102. 2002..Thus Ras-Raf binding in response to activation of Ras-coupled receptors may utilize Raf protein that is already present at the membrane...
B-Raf/Rap1 signaling, but not c-Raf-1/Ras, induces the histidine decarboxylase promoter in Helicobacter pylori infectionSilja Wessler
, Abt. Molekulare Biologie, Berlin, Germany
FASEB J 16:417-9. 2002..pylori with gastric epithelial cells and help to define potential molecular targets for therapeutic interventions in the context of H. pylori-related gastric diseases...
The farnesyltransferase inhibitor R115777 (ZARNESTRA) enhances the pro-apoptotic activity of interferon-alpha through the inhibition of multiple survival pathwaysMichele Caraglia
Experimental Pharmacology Unit, Experimental Oncology Department, National Cancer Institute Fondazione G Pascale, Naples, Italy
Int J Cancer 121:2317-30. 2007....
B- and C-RAF display essential differences in their binding to Ras: the isotype-specific N terminus of B-RAF facilitates Ras bindingAndreas Fischer
Institut fur Medizinische Strahlenkunde und Zellforschung, University of Wuerzburg, 97078 Wuerzburg, Germany
J Biol Chem 282:26503-16. 2007..Taken together, these data suggest that the activation of B-RAF, in contrast to C-RAF, may take place both at the plasma membrane and in the cytosolic environment...
Unique N-region determines low basal activity and limited inducibility of A-RAF kinase: the role of N-region in the evolutionary divergence of RAF kinase function in vertebratesAngela Baljuls
Institute for Medical Radiation and Cell Research, University of Wuerzburg, 97078 Wuerzburg, Germany
J Biol Chem 282:26575-90. 2007..Considering this observation, we suggest that tyrosine 296, which is unique for A-RAF, is a major determinant of the low activating potency of this RAF isoform...
Immunogenicity of constitutively active V599EBRafMads Hald Andersen
Insitute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
Cancer Res 64:5456-60. 2004....
MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1Jan Willem Voncken
Research Institute Growth and Development, Molecular Genetics, Maastricht University, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands
J Biol Chem 280:5178-87. 2005..This suggests a novel mechanism by which a silenced gene status can be modulated and implicates PcG-mediated repression as a dynamically controlled process...
Validation of a liquid chromatography assay for the quantification of the Raf kinase inhibitor BAY 43-9006 in small volumes of mouse serumSamar Afify
, , Am Hubland, , Germany
J Chromatogr B Analyt Technol Biomed Life Sci 809:99-103. 2004..The lower limit of quantitation (LOQ) was 80 ng/ml with an accuracy of 105.8%. Thus, this method has been validated and can be applied for the drug monitoring or pharmacokinetic studies of BAY 43-9006 in small volumes of serum samples...
Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomesRobert Kurzbauer
Institute for Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
Proc Natl Acad Sci U S A 101:10984-9. 2004..Taken together, the presented work provides insight into the spatial regulation of MAPK signaling, illustrating how p14 and MP1 collaborate as an endosomal adaptor/scaffold complex...
Bag1 is essential for differentiation and survival of hematopoietic and neuronal cellsRudolf Götz
Institut für Klinische Neurobiologie, University of Wurzburg, Josef Schneider Str 11, D 97080 Wurzburg, Germany
Nat Neurosci 8:1169-78. 2005..Our data show that Bag1 is a physiological mediator of extracellular survival signals linked to the cellular mechanisms that prevent apoptosis in hematopoietic and neuronal progenitor cells...
B-Raf and C-Raf signaling investigated in a simplified model of the mitogenic kinase cascadeArmin Robubi
Department of Bioinformatics, University of Wuerzburg, D-97074 Wuerzburg, Germany
Biol Chem 386:1165-71. 2005....
Dynamic changes in C-Raf phosphorylation and 14-3-3 protein binding in response to growth factor stimulation: differential roles of 14-3-3 protein binding sitesMirko Hekman
Institute for Medical Radiation and Cell Research, University of Wuerzburg, 97078 Wuerzburg
J Biol Chem 279:14074-86. 2004..14-3-3 binding epitopes pS259 and pS621 and visualized for the first time the sequence of the essential C-Raf phosphorylation events in mammalian cells in response to growth factor stimulation...
Reversible membrane interaction of BAD requires two C-terminal lipid binding domains in conjunction with 14-3-3 protein bindingMirko Hekman
Institute for Medical Radiation and Cell Research and Institute for Clinical Neurobiology, University of Wuerzburg, 97078 Wuerzburg, Germany
J Biol Chem 281:17321-36. 2006..The dynamic interaction of BAD with membranes is tied to activation and membrane translocation of Bcl-XL...
Ras oncogenes and their downstream targetsKrishnaraj Rajalingam
University of Wurzburg, Institut fur Medizinische Strahlenkunde und Zellforschung, Versbacherstr 5, D 97078 Wurzburg, Germany
Biochim Biophys Acta 1773:1177-95. 2007..Finally, we comment on the role of micro RNAs in modulating RAS expression, contribution of RAS to stem cell function and on high-throughput analyses of RAS signaling networks...
Vivotif--a 'magic shield' for protection against typhoid fever and delivery of heterologous antigensIvaylo Gentschev
Berna Biotech Ltd, Berne, Switzerland
Chemotherapy 53:177-80. 2007..Recently, we successfully used Ty21a for antigen delivery via the haemolysin secretion system of Escherichia coli, which allows efficient protein secretion from the carrier bacteria...
Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migrationKrishnaraj Rajalingam
Department of Molecular Biology, Max Planck Institute for Infection Biology, Schumannstrasse 21 22, D 10117 Berlin, Germany
Nat Cell Biol 7:837-43. 2005..Our data show an unexpected role of prohibitin in the activation of the Ras-Raf signalling pathway and in modulating epithelial cell adhesion and migration...
Mitogen-activated 3p kinase is active in the nucleusVera Zakowski
Institut für Molekulare Medizin IMM, Heinrich Heine Universitat Dusseldorf, D 40225 Dusseldorf, Germany
Exp Cell Res 299:101-9. 2004..These data not only show that nuclear export of the kinase is mechanistically uncoupled from its activation, but also provide a novel mechanism by which cells may modulate enzyme activity toward a stimulus-specific response...
Cortical migration defects in mice expressing A-RAF from the B-RAF locusGuadalupe Camarero
Institut fur Medizinische Strahlenkunde und Zellforschung, Bayerische Julius Maximilians Universität, Versbacher Str 5, D 97078 Wurzburg, Germany
Mol Cell Biol 26:7103-15. 2006..Our data reveal that B-RAF is an important mediator of neuronal survival, migration, and dendrite formation and that A-RAF cannot fully compensate for these functions...
Raf and the road to cell survival: a tale of bad spells, ring bearers and detoursJakob Troppmair
Department of General and Transplantation Surgery, Daniel Swarovski Research Lab, University of Innsbruck, Innsbruck, Austria
Biochem Pharmacol 66:1341-5. 2003..They include the recruitment of novel effectors such as IAP and Bcl-2 proteins, key molecules in cell survival control, which interfere with the executions of the cell death at various levels, but also direct effects on metabolic events...
Lung-specific expression of active Raf kinase results in increased mortality of influenza A virus-infected miceVeronika Olschläger
Institut fur Immunologie, Bundesforschungsanstalt fur Viruskrankheiten der Tiere, Paul Ehrlich Str 28, Tubingen, Germany
Oncogene 23:6639-46. 2004..These findings disclose the possibility to use modified influenza virus for the therapy of tumors with an activated Ras/Raf signalling pathway...
Diverse effects of RacV12 on cell transformation by Raf: partial inhibition of morphological transformation versus deregulation of cell cycle controlEugen Kerkhoff
, , Versbacher Strasse 5, , Germany
Biochim Biophys Acta 1589:151-9. 2002..These results indicate a pro-oncogenic function of the Rac GTPase with respect to the deregulation of cell cycle control...
Regulation of pyruvate kinase type M2 by A-Raf: a possible glycolytic stop or go mechanismSybille Mazurek
Institute of Biochemistry and Endocrinology, Veterinary Faculty, Justus Liebig University, Giessen, Germany
Anticancer Res 27:3963-71. 2007..High serine levels thus may be responsible for the activation of M2-PK in A-Raf transformed NIH3T3 cells...
Novel C-Raf phosphorylation sites: serine 296 and 301 participate in Raf regulationMirko Hekman
Institut fuer Medizinische Strahlenkunde und Zellforschung, University of Wuerzburg, 97078 Wuerzburg, Germany
FEBS Lett 579:464-8. 2005..Furthermore, we show here, using point mutant forms of C-Raf kinases with serine to alanine and serine to aspartic acid substitution, that serines 296 and 301 contribute to negative regulation of C-Raf...
