TY - JOUR A1 - Simböck, Elisabeth A1 - Marksteiner, Jessica A1 - Machacek, Thomas A1 - Wiessner, Katharina A1 - Gepp, Barbara A1 - Jesenberger, Veronika A1 - Weihs, Anna A1 - Leitner, Rita T1 - The Power of Problem Based Learning beyond its Didactic Attributes JF - Journal of Problem Based Learning in Higher Education (JPBLHE) N2 - Hybrid courses with a focus on practice-orientated education and self-guided learning phases are on the rise on the higher education sector. Disciplines in Life Sciences implicate a high degree of practical laboratory expertise. The University of Applied Sciences (UAS) in Vienna, Austria, has thus been endeavoured offering students a high qualitative education integrating hybrid courses based on PBL principles, which consist of on-site (including the transmission of necessary background and practical laboratory training) and off-site (including self-study phases) sessions. As practical laboratory units are central in those courses, the restrictive measures, including the transition to a complete online teaching format due to the first Covid-19-pandemic lock-down, had severe effects on the implementation and the quality of the curriculum. According to surveys made specifically to address this problematic situation, it can be concluded that on-site practical units are fundamental for certain disciplines such as Life Sciences. KW - Problem-based Learning KW - Life Science didactics KW - Hybrid PBL-methods KW - COVID-19 KW - Life Science Education Y1 - VL - 9 IS - 1 SP - 109 EP - 130 ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Zmajkovicova, Katarina A1 - Catalanotti, Federica A1 - Baumgartner, Christian A1 - Reyes, Gloria Ximena A1 - Baccarini, Manuela T1 - MEK1 is required for PTEN membrane recruitment, AKT regulation, and the maintenance of peripheral tolerance JF - Mol. Cell N2 - The Raf/MEK/ERK and PI3K/Akt pathways are prominent effectors of oncogenic Ras. These pathways negatively regulate each other, but the mechanism involved is incompletely understood. We now identify MEK1 as an essential regulator of lipid/protein phosphatase PTEN, through which it controls phosphatidylinositol-3-phosphate accumulation and AKT signaling. MEK1 ablation stabilizes AKT activation and, in vivo, causes a lupus-like autoimmune disease and myeloproliferation. Mechanistically, MEK1 is necessary for PTEN membrane recruitment as part of a ternary complex containing the multidomain adaptor MAGI1. Complex formation is independent of MEK1 kinase activity but requires phosphorylation of T292 on MEK1 by activated ERK. Thus, inhibiting the ERK pathway reduces PTEN membrane recruitment, increasing phosphatidylinositol-3-phosphate accumulation and AKT activation. Our data offer a conceptual framework for the observation that activation of the PI3K pathway frequently mediate resistance to MEK inhibitors and for the promising results obtained by combined MEK/PI3K inhibition in preclinical cancer models. KW - MEK1 pathway KW - membrane recruitment KW - preclinical cancer models Y1 - 2020 VL - 2013 IS - 50 SP - 43 EP - 55 ER - TY - CHAP A1 - Nebel, Sabrina A1 - Salado Manzano, Cristina A1 - Just, Valentin A1 - Leeb, Christine A1 - Jesenberger, Veronika T1 - Role of the MEK/ERK pathway in chondrogenic differentiation: Establishment of a protocol for the generation of MEK1-knockout hTERT ASCs and assessment of their differentiation potential T2 - Proceedings des Forschungsforum 2017 der österreichischen Fachhochschulen KW - Chondrogenesis Y1 - 2018 ER - TY - GEN A1 - Nebel, Sabrina A1 - Salado Manzano, Cristina A1 - Just, Valentin A1 - Leeb, Christine A1 - Jesenberger, Veronika T1 - Role of the MEK/ERK pathway in chondrogenic differentiation: Establishment of a protocol for the generation of MEK1-knockout hTERT ASCs and assessment of their differentiation potential KW - Chondrogenesis Y1 - 2018 ER - TY - JOUR A1 - Catalanotti, Federica A1 - Reyes, Gloria Ximena A1 - Jesenberger, Veronika A1 - Galabova-Kovacs, Gergana A1 - de Matos Simoes, Ricardo A1 - Carugo, Oliviero A1 - Baccarini, Manuela T1 - A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal JF - Nat Struct Mol Biol. N2 - Mek1 and Mek2 (also known as Map2k1 and Map2k2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling. Here we describe a previously uncharacterized, unexpected role of Mek1 in downregulating Mek2-dependent Erk signaling. Mek1 mediates the regulation of Mek2 in the context of a previously undiscovered Mek1-Mek2 complex. The Mek heterodimer is negatively regulated by Erk-mediated phosphorylation of Mek1 on Thr292, a residue missing in Mek2. Disabling this Erk-proximal negative-feedback step stabilizes the phosphorylation of both Mek2 and Erk in cultured cells and in vivo in Mek1 knockout embryos and mice. Thus, in disagreement with the current perception of the pathway, the role of Mek1 and Mek2 in growth factor-induced Erk phosphorylation is not interchangeable. Our data establish Mek1 as the crucial modulator of Mek and Erk signaling and have potential implications for the role of Mek1 and Mek2 in tumorigenesis. KW - Mek1-Mek2 pathway KW - tumorigenesis KW - ERK activation KW - cancer biology Y1 - 2020 VL - 2009 IS - 16(3) SP - 294 EP - 303 ER - TY - JOUR A1 - Krautwald, Stefan A1 - Büscher, Dirk A1 - Jesenberger, Veronika A1 - Buder, Sylke A1 - Baccarini, Manuela T1 - Involvement of the protein tyrosine phosphatase SHP-1 in Ras-mediated activation of the mitogen-activated protein kinase pathway. JF - Mol Cell Biol. N2 - Ubiquitously expressed SH2-containing tyrosine phosphatases interact physically with tyrosine kinase receptors or their substrates and relay positive mitogenic signals via the activation of the Ras-mitogen-activated protein kinase (MAPK) pathway. Conversely, the structurally related phosphatase SHP-1 is predominantly expressed in hemopoietic cells and becomes tyrosine phosphorylated upon colony-stimulating factor 1 treatment of macrophages without associating with the colony-stimulating factor 1 receptor tyrosine kinase. Mice lacking functional SHP-1 (me/me and me(v)/me(v)) develop systemic autoimmune disease with accumulation of macrophages, suggesting that SHP-1 may be a negative regulator of hemopoietic cell growth. By using macrophages expressing dominant negative Ras and the me(v)/me(v) mouse mutant, we show that SHP-1 is activated in the course of mitogenic signal transduction in a Ras-dependent manner and that its activity is necessary for the Ras-dependent activation of the MAPK pathway but not of the Raf-1 kinase. Consistent with a role for SHP-1 as an intermediate between Ras and the MEK-MAPK pathway, Ras-independent activation of the latter kinases by bacterial lipopolysaccharide occurred normally in me(v)/me(v) cells. Our results sharply accentuate the diversity of signal transduction in mammalian cells, in which the same signaling intermediates can be rearranged to form different pathways. KW - Molecular Cell Biology KW - protein kinase pathway KW - Ras Y1 - 2020 U6 - http://dx.doi.org/doi: 10.1128/mcb.16.11.5955 VL - 1996 IS - 16(11) SP - 5955 EP - 5963 ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Procyk, Katarzyna A1 - Yuan, Junying A1 - Reipert, Siegfried A1 - Baccarini, Manuela T1 - Salmonella-induced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis JF - J Exp Med. N2 - The enterobacterial pathogen Salmonella induces phagocyte apoptosis in vitro and in vivo. These bacteria use a specialized type III secretion system to export a virulence factor, SipB, which directly activates the host's apoptotic machinery by targeting caspase-1. Caspase-1 is not involved in most apoptotic processes but plays a major role in cytokine maturation. We show that caspase-1-deficient macrophages undergo apoptosis within 4-6 h of infection with invasive bacteria. This process requires SipB, implying that this protein can initiate the apoptotic machinery by regulating components distinct from caspase-1. Invasive Salmonella typhimurium targets caspase-2 simultaneously with, but independently of, caspase-1. Besides caspase-2, the caspase-1-independent pathway involves the activation of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none of which occurs during caspase-1-dependent apoptosis. By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1-dependent and -independent apoptosis. Particularly, activation of caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2. The ability of Salmonella to induce caspase-1-independent macrophage apoptosis may play a role in situations in which activation of this protease is either prevented or uncoupled from the induction of apoptosis. KW - caspase-2 activation in macrophages KW - pathogen-activated apoptosis KW - Molecular Cell Biology Y1 - 2020 U6 - http://dx.doi.org/10.1084/jem.192.7.1035 VL - 2000 IS - 192(7) SP - 1035 EP - 1046 ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Procyk, Katarzyna A1 - Rüth, Jochen A1 - Schreiber, Martin A1 - Theussl, Hans Christian A1 - Wagner, Erwin A1 - Baccarini, Manuela T1 - Protective Role of Raf-1 in Salmonella-Induced Macrophage Apoptosis JF - J Exp Med. N2 - 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 degradation of Raf-1, an important intermediate in macrophage proliferation and activation. Raf-1 degradation is SipB- and caspase-1–dependent, and is prevented by proteasome inhibitors. To study the functional significance of Raf-1 in this process, the c-raf-1 gene was inactivated by Cre-loxP–mediated recombination in vivo. Macrophages lacking c-raf-1 are hypersensitive towards pathogen-induced apoptosis. Surprisingly, activation of the antiapoptotic mitogen-activated protein kinase kinase (MEK)/extracellular signal–regulated kinase (ERK) and nuclear factor κB pathways is normal in Raf-1–deficient macrophages, and mitochondrial fragility is not increased. Instead, pathogen-mediated activation of caspase-1 is enhanced selectively, implying that Raf-1 antagonizes stimulus-induced caspase-1 activation and apoptosis. KW - Salmonella-Induced Macrophage Apoptosis KW - Raf-1 pathway KW - Molecular Cell Biology Y1 - 2020 U6 - http://dx.doi.org/10.1084/jem.193.3.353 VL - 2001 IS - 193(3) SP - 353 EP - 364 ER - TY - JOUR A1 - Jesenberger, Veronika A1 - Jentsch, Stefan T1 - Deadly encounter: ubiquitin meets apoptosis JF - Nat Rev Mol Cell Biol. N2 - The ubiquitin/proteasome pathway is the main non-lysosomal route for intracellular protein degradation in eukaryotes. It is instrumental to various cellular processes, such as cell-cycle progression, transcription and antigen processing. Recent findings also substantiate a pivotal role of the ubiquitin/proteasome pathway in the regulation of apoptosis. Regulatory molecules that are involved in programmed cell death have been identified as substrates of the proteasome. Moreover, key regulators of apoptosis themselves seem to have an active part in the proteolytic inactivation of death executors. KW - programmed cell death KW - Molecular Cell Biology Y1 - 2020 U6 - http://dx.doi.org/https://doi.org/10.1038/nrm731 VL - 2002 IS - 3(2) SP - 112 EP - 121 ER - TY - JOUR A1 - Leeb, Christine A1 - Leitner, Rita A1 - Pichler, Verena A1 - Huber-Gries, Carina A1 - Rünzler, Dominik A1 - Jesenberger, Veronika T1 - Einführung und Optimierung eines praxisorientierten PBL-Moduls im Life-Science-Bereich JF - Zeitschrift für Hochschulentwicklung (ZFHE) KW - Life Science KW - Problem Based Learning KW - Education Y1 - 2018 VL - 11 IS - 3 SP - 107 EP - 121 ER - TY - CHAP A1 - Leeb, Christine A1 - Leitner, Rita A1 - Pichler, Verena A1 - Huber-Gries, Carina A1 - Rünzler, Dominik A1 - Jesenberger, Veronika T1 - Einführung und Optimierung eines praxisorientierten PBL-Moduls im Life-Science-Bereich T2 - Proceedings des Kongresses Problem-Based Learning 2016 PBL - Kompetenzen fördern, Zukunft gestalten KW - Life Science KW - Problem Based Learning KW - Education Y1 - 2018 ER - TY - GEN A1 - Leeb, Christine A1 - Leitner, Rita A1 - Pichler, Verena A1 - Huber-Gries, Carina A1 - Rünzler, Dominik A1 - Jesenberger, Veronika T1 - Einführung und Optimierung eines praxisorientierten PBL-Moduls im Life-Science-Bereich KW - Life Science KW - Problem Based Learning KW - Education Y1 - 2018 ER -