TNF{alpha} shedding and epidermal inflammation are controlled by Jun proteins (2009)
Guinea-Viniegra, Juan, Zenz, Rainer, Scheuch, Harald, Hnisz, Denes, Holcmann, Martin, Bakiri, Latifa, ...
Inducible epidermal deletion of JunB and c-Jun in adult mice causes a psoriasis-like inflammatory skin disease. Increased levels of the proinflammatory cytokine TNFα play a major role in this...
Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease (2008)
Zenz, Rainer, Eferl, Robert, Scheinecker, Clemens, Redlich, Kurt, Smolen, Josef, Schonthaler, Helia B, ...
Abstract Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in...
Hanahan, Douglas, Wagner, Erwin F., Palmiter, Richard D.
This perspective describes the concurrent development in the 1980s of the first transgenic mice genetically engineered to express dominant oncogenes, involving independent researchers who were...
Distinct functions of junD in cardiac hypertrophy and heart failure (2005)
Ricci, Romeo, Eriksson, Urs, Oudit, Gavin Y., Eferl, Robert, Akhmedov, Alexander, Sumara, Izabela, ...
Cardiac hypertrophic stimuli induce both adaptive and maladaptive growth response pathways in heart. Here we show that mice lacking junD develop less adaptive hypertrophy in heart after mechanical...
Gass, Peter, Fleischmann, Alexander, Hvalby, Øivind, Jensen, Vidar, Zacher, Christiane, Strekalova, Tatyana, ...
The immediate early gene c−fos is part of the AP−1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c−Fos in the brain show...
Sprengel, Rolf, Spanagel, Rainer, Kvello, Ane, Layer, Liliana, Zacher, Christiane, Strekalova, Tatyana, ...
The immediate early gene c-fos is part of the activator protein-1 transcription factor and has been postulated to participate in the molecular mechanisms of learning and memory. To test this...
Fleischmann, Alexander, Hvalby, Øyvind, Jensen, Vidar, Strekalova, Tatyana, Zacher, Christiane, Layer, Liliana, ...
Long-term learning and memory require long-lasting changes in the strength of specific synaptic connections between neurons (Martin et al., 2000; Kandel, 2001). These adaptive changes in synaptic...
Haigh, Jody J, Morelli, Paula I, Gerhardt, Holger, Haigh, Katharina, Tsien, John, Damert, Annette, ...
To determine the function of VEGF-A in nervous system development, we have utilized the Nestin promoter-driven Cre recombinase transgene, in conjunction with a conditional and hypomorphic VEGF-A...
Schausberger, Elisabeth, Eferl, Robert, Parzefall, Wolfram, Chabikovsky, Monica, Breit, Paul, Wagner, Erwin F., ...
For growth stimulation of liver cells by hepatocyte growth factor (HGF) or transforming growth factor α (TGFα) via receptor tyrosine kinases, c-fos/c-jun has been considered a point of intersection...
Schausberger, Elisabeth, Eferl, Robert, Parzefall, Wolfram, Chabikovsky, Monica, Breit, Paul, Wagner, Erwin F., ...
For growth stimulation of liver cells by hepatocyte growth factor (HGF) or transforming growth factor α (TGFα) via receptor tyrosine kinases, c-fos/c-jun has been considered a point of...
Schausberger, Elisabeth, Eferl, Robert, Parzefall, Wolfram, Chabicovsky, Monika, Breit, Paul, Wagner, Erwin F., ...
Schausberger, Elisabeth, Eferl, Robert, Parzefall, Wolfram, Chabikovsky, Monica, Breit, Paul, Wagner, Erwin F., ...
For growth stimulation of liver cells by hepatocyte growth factor (HGF) or transforming growth factor α (TGFα) via receptor tyrosine kinases, c-fos/c-jun has been considered a point of intersection...
Fra-1 replaces c-Fos-dependent functions in mice (2000)
Fleischmann, Alexander, Hafezi, Farhad, Elliott, Candace, Remé, Charlotte E., Rüther, Ulrich, Wagner, Erwin F.
Control of cell cycle progression by c-Jun is p53 dependent (1999)
Schreiber, Martin, Kolbus, Andrea, Piu, Fabrice, Szabowski, Axel, Möhle-Steinlein, Uta, Tian, Jianmin, ...
PARP is important for genomic stability but dispensable in apoptosis (1997)
Wang, Zhao-Qi, Stingl, Laura, Morrison, Ciaran, Jantsch, Michael, Los, Marek, Schulze-Osthoff, Klaus, ...
Rüther, Ulrich, Tripodi, Marco, Cortcsc, Riccardo, Wagner, Erwin F.
α-1-antitrypsin (α-1AT) present in large amounts in human serum and synthesized predominantly in hepatocytes, is the most abundant protease inhibitor and α-1AT mutant proteins are associated with...
Behrens, Axel, Sabapathy, Kanaga, Graef, Isabella, Cleary, Mike, Crabtree, Gerald R., Wagner, Erwin F.
The Jun N-terminal kinases (JNKs) recently have been shown to be required for thymocyte apoptosis and T cell differentiation and/or proliferation. To investigate the molecular targets of JNK...
Kolbus, Andrea, Herr, Ingrid, Schreiber, Martin, Debatin, Klaus-Michael, Wagner, Erwin F., Angel, Peter
Mouse 3T3 fibroblasts derived from fetuses lacking c-Jun were used to define an essential role of c-Jun, a main component of the transcription factor AP-1, in the cellular response to the alkylating...
Behrens, Axel, Sibilia, Maria, David, Jean-Pierre, Möhle-Steinlein, Uta, Tronche, François, Schütz, Günther, ...
Mice lacking the AP-1 transcription factor c-jun die at mid-gestation showing heart defects and impaired hepatogenesis. To inactivate c-jun in hepatocytes, mice carrying a floxed c-jun allele were...
Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene
Mikula, Mario, Schreiber, Martin, Husak, Zvenislava, Kucerova, Lucia, Rüth, Jochen, Wieser, Rotraud, ...
The Raf kinases play a key role in relaying signals elicited by mitogens or oncogenes. Here, we report that c-raf-1–/– embryos are growth retarded and die at midgestation with anomalies in the...
Promoter Specificity and Biological Activity of Tethered AP-1 Dimers
Bakiri, Latifa, Matsuo, Koichi, Wisniewska, Marta, Wagner, Erwin F., Yaniv, Moshe
Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of Jun, Fos, and ATF family proteins. Both gain- and loss-of-function studies have revealed specific roles for...
Osteoclasts are essential for TNF-α–mediated joint destruction
Redlich, Kurt, Hayer, Silvia, Ricci, Romeo, David, Jean-Pierre, Tohidast-Akrad, Makiyeh, Kollias, George, ...
The detailed cellular and molecular mechanisms leading to joint destruction in rheumatoid arthritis, a disease driven by proinflammatory cytokines, are still unknown. To address the question of...
JNK phosphorylation relieves HDAC3-dependent suppression of the transcriptional activity of c-Jun
Weiss, Carsten, Schneider, Sandra, Wagner, Erwin F., Zhang, Xiaohong, Seto, Edward, Bohmann, Dirk
The AP-1 transcription factor c-Jun is a prototypical nuclear effector of the JNK signal transduction pathway. The integrity of JNK phosphorylation sites at serines 63/73 and at threonines 91/93 in...
JunB suppresses cell proliferation by transcriptional activation of p16INK4a expression
Passegué, Emmanuelle, Wagner, Erwin F.
A role for the transcription factor JunB in proliferation control was investigated in genetically modified mouse fibroblasts. Increased JunB expression induced high levels of the cyclin-dependent...
Control of cell cycle progression by c-Jun is p53 dependent
Schreiber, Martin, Kolbus, Andrea, Piu, Fabrice, Szabowski, Axel, Möhle-Steinlein, Uta, Tian, Jianmin, ...
The c-jun proto-oncogene encodes a component of the mitogen-inducible immediate–early transcription factor AP-1 and has been implicated as a positive regulator of cell proliferation and...
PARP is important for genomic stability but dispensable in apoptosis
Wang, Zhao-Qi, Stingl, Laura, Morrison, Ciaran, Jantsch, Michael, Los, Marek, Schulze-Osthoff, Klaus, ...
Mice lacking the gene encoding poly(ADP-ribosyl) transferase (PARP or ADPRT) display no phenotypic abnormalities, although aged mice are susceptible to epidermal hyperplasia and obesity in a mixed...
Fra-1 replaces c-Fos-dependent functions in mice
Fleischmann, Alexander, Hafezi, Farhad, Elliott, Candace, Remé, Charlotte E., Rüther, Ulrich, Wagner, Erwin F.
Structure–function analysis as well as studies with knock-out and transgenic mice have assigned distinct functions to c-Fos and Fra-1, two components of the transcription factor AP-1 (activator...
Pellicer, Angel, Wagner, Erwin F., Kareh, Adele El, Dewey, Michael J., Reuser, Arnold J., Silverstein, Saul, ...
Teratocarcinoma (TCC) stem cells provide unique prospects for the introduction of specific genes into mice, by virtue of their dual capacity for propagation in vitro and for normal differentiation in...
JunD regulates lymphocyte proliferation and T helper cell cytokine expression
Meixner, Arabella, Karreth, Florian, Kenner, Lukas, Wagner, Erwin F
Transgenic mice broadly expressing JunD (Ubi-junDm) appear phenotypically normal, but have strongly reduced numbers of peripheral lymphocytes. JunD overexpression in lymphocytes does not protect from...
The Fos-related antigen Fra-1 is an activator of bone matrix formation
Eferl, Robert, Hoebertz, Astrid, Schilling, Arndt F, Rath, Martina, Karreth, Florian, Kenner, Lukas, ...
Ectopic expression of the transcription factor Fra-1 in transgenic mice leads to osteosclerosis, a bone disorder characterized by increased bone mass. The molecular basis for this phenotype is...
Distinct functions of junD in cardiac hypertrophy and heart failure
Ricci, Romeo, Eriksson, Urs, Oudit, Gavin Y., Eferl, Robert, Akhmedov, Alexander, Sumara, Izabela, ...
Cardiac hypertrophic stimuli induce both adaptive and maladaptive growth response pathways in heart. Here we show that mice lacking junD develop less adaptive hypertrophy in heart after mechanical...
Essential role of RSK2 in c-Fos–dependent osteosarcoma development
David, Jean-Pierre, Mehic, Denis, Bakiri, Latifa, Schilling, Arndt F., Mandic, Vice, Priemel, Matthias, ...
Inactivation of the growth factor–regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here...
JNK1 is not essential for TNF-mediated joint disease
Köller, Marcus, Hayer, Silvia, Redlich, Kurt, Ricci, Romeo, David, Jean-Pierre, Steiner, Günter, ...
Tumour necrosis factor (TNF) signalling molecules are considered as promising therapeutic targets of antirheumatic therapy. Among them, mitogen-activated protein kinases are thought to be of central...
Verrecchia, Franck, Wagner, Erwin F., Mauviel, Alain
We used a gene knockout approach to elucidate the specific roles played by the Jun-N-terminal kinase (JNK) and NF-κB pathways downstream of TNF-α in the context of α(2) type I collagen gene...
Stoll, Stefan W, Kansra, Sanjay, Peshick, Scott, Fry, David W, Leopold, Wilbur R, Wiesen, Jane F, ...
Induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA in mouse skin organ culture was blocked by two pan-ErbB receptor tyrosine kinase (RTK) inhibitors but not by...
c-Jun/AP-1 controls liver regeneration by repressing p53/p21 and p38 MAPK activity
Stepniak, Ewa, Ricci, Romeo, Eferl, Robert, Sumara, Grzegorz, Sumara, Izabela, Rath, Martina, ...
The AP-1 transcription factor c-Jun is a key regulator of hepatocyte proliferation. Mice lacking c-Jun in the liver (c-jun Δli*) display impaired liver regeneration after partial hepatectomy (PH)....
Neuronal survival depends on EGFR signaling in cortical but not midbrain astrocytes
Wagner, Bettina, Natarajan, Anuradha, Grünaug, Sabine, Kroismayr, Renate, Wagner, Erwin F, Sibilia, Maria
Mice lacking epidermal growth factor receptor (EGFR) develop a neurodegeneration of unknown etiology affecting exclusively the frontal cortex and olfactory bulbs. Here, we show that EGFR signaling...
Perdiguero, Eusebio, Ruiz-Bonilla, Vanessa, Gresh, Lionel, Hui, Lijian, Ballestar, Esteban, Sousa-Victor, Pedro, ...
The p38 mitogen-activated protein kinase (MAPK) pathway plays a critical role in skeletal muscle differentiation. However, the relative contribution of the four p38 MAPKs (p38α, p38β, p38γ and...
Besirli, Cagri G., Wagner, Erwin F., Johnson, Eugene M.
c-Jun is induced in many neuronal death paradigms. A critical step in c-Jun regulation involves phosphorylation of Ser63/Ser73 located in the NH2-terminal transactivation domain. To determine the...
Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects
Kenner, Lukas, Hoebertz, Astrid, Beil, Timo, Keon, Niamh, Karreth, Florian, Eferl, Robert, ...
Because JunB is an essential gene for placentation, it was conditionally deleted in the embryo proper. JunBΔ/Δ mice are born viable, but develop severe low turnover osteopenia caused by apparent...
Ruocco, Maria Grazia, Maeda, Shin, Park, Jin Mo, Lawrence, Toby, Hsu, Li-Chung, Cao, Yixue, ...
Transcription factor, nuclear factor κB (NF-κB), is required for osteoclast formation in vivo and mice lacking both of the NF-κB p50 and p52 proteins are osteopetrotic. Here we address the...
CD44 is a determinant of inflammatory bone loss
Hayer, Silvia, Steiner, Günter, Görtz, Birgit, Reiter, Erika, Tohidast-Akrad, Makiyeh, Amling, Michael, ...
Chronic inflammation is a major trigger of local and systemic bone loss. Disintegration of cell–matrix interaction is a prerequisite for the invasion of inflammatory tissue into bone. CD44 is a...
Autoamplification of NFATc1 expression determines its essential role in bone homeostasis
Asagiri, Masataka, Sato, Kojiro, Usami, Takako, Ochi, Sae, Nishina, Hiroshi, Yoshida, Hiroki, ...
NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide...
Sabapathy, Kanaga, Kallunki, Tuula, David, Jean-Pierre, Graef, Isabella, Karin, Michael, Wagner, Erwin F.
Apoptotic and mitogenic stimuli activate c-Jun NH2-terminal kinases (JNKs) in T cells. Although T cells express both JNK1 and JNK2 isozymes, the absence of JNK2 alone can result in resistance to...
Protective Role of Raf-1 in Salmonella-Induced Macrophage Apoptosis
Jesenberger, Veronika, Procyk, Katarzyna J., Rüth, Jochen, Schreiber, Martin, Theussl, Hans-Christian, Wagner, Erwin F., ...
Invasive Salmonella induces macrophage apoptosis via the activation of caspase-1 by the bacterial protein SipB. Here we show that infection of macrophages with Salmonella causes the activation and...
Hasselblatt, Peter, Rath, Martina, Komnenovic, Vukoslav, Zatloukal, Kurt, Wagner, Erwin F.
Analysis of the molecular factors determining hepatocyte survival or death in response to inflammatory stimuli is essential for understanding the pathogenesis of inflammatory liver disease and for...
Functions of c-Jun in Liver and Heart Development
Eferl, Robert, Sibilia, Maria, Hilberg, Frank, Fuchsbichler, Andrea, Kufferath, Iris, Guertl, Barbara, ...
Mice lacking the AP-1 transcription factor c-Jun die around embryonic day E13.0 but little is known about the cell types affected as well as the cause of embryonic lethality. Here we show that a...
Sabapathy, Kanaga T., Pepper, Michael S., Kiefer, Friedemann, Möhle-Steinlein, Uta, Tacchini-Cottier, Fabienne, Fetka, Ingrid, ...
The middle T antigen of murine Polyomavirus (PymT) rapidly transforms endothelial cells, leading to the formation of vascular tumors in newborn mice. Transformed endothelial (End.) cell lines...
Heumann, Rolf, Goemans, Christoph, Bartsch, Daniela, Lingenhöhl, Kurt, Waldmeier, Peter C., Hengerer, Bastian, ...
Ras is a universal eukaryotic intracellular protein integrating extracellular signals from multiple receptor types. To investigate its role in the adult central nervous system, constitutively...
Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease
Zenz, Rainer, Eferl, Robert, Scheinecker, Clemens, Redlich, Kurt, Smolen, Josef, Schonthaler, Helia B, ...
Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse...
Jiao, Xuanmao, Katiyar, Sanjay, Liu, Manran, Mueller, Susette C., Lisanti, Michael P., Li, Anping, ...
The spread of metastatic tumors to different organs is associated with poor prognosis. The metastatic process requires migration and cellular invasion. The protooncogene c-jun encodes the founding...
JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells
Gurzov, Esteban N., Ortis, Fernanda, Bakiri, Latifa, Wagner, Erwin F., Eizirik, Decio L.
Cytokines contribute to pancreatic β-cell apoptosis in type 1 diabetes (T1D) by modulation of β-cell gene expression networks. The transcription factor Activator Protein-1 (AP-1) is a key regulator...
Wolter, Sabine, Doerrie, Anneke, Weber, Axel, Schneider, Heike, Hoffmann, Elke, Von Der Ohe, Juliane, ...
Interleukin-1 (IL-1)-induced mRNA expression of ccl2 (also called MCP-1), a prototypic highly regulated inflammatory gene, is severely suppressed in cells lacking c-Jun or Jun N-terminal protein...
Hui, Lijian, Zatloukal, Kurt, Scheuch, Harald, Stepniak, Ewa, Wagner, Erwin F.
JNK proteins have been shown to be involved in liver carcinogenesis in mice, but the extent of their involvement in the development of human liver cancers is unknown. Here, we show that activation of...
Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1
Eferl, Robert, Hasselblatt, Peter, Rath, Martina, Popper, Helmut, Zenz, Rainer, Komnenovic, Vukoslav, ...
Studies using genetically modified mice have revealed fundamental functions of the transcription factor Fos/AP-1 in bone biology, inflammation, and cancer. However, the biological role of the...
Sibilia, Maria, Wagner, Erwin F.
Transgenic animals are organisms in which permanent gene modifications have been experimentally introduced into their germline. Most knowledge of modern biology relating to the tissue-specific...