@article{SimboeckMarksteinerMachaceketal., author = {Simb{\"o}ck, Elisabeth and Marksteiner, Jessica and Machacek, Thomas and Wiessner, Katharina and Gepp, Barbara and Jesenberger, Veronika and Weihs, Anna and Leitner, Rita}, title = {The Power of Problem Based Learning beyond its Didactic Attributes}, series = {Journal of Problem Based Learning in Higher Education (JPBLHE)}, volume = {9}, journal = {Journal of Problem Based Learning in Higher Education (JPBLHE)}, number = {1}, pages = {109 -- 130}, abstract = {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.}, subject = {Problem-based Learning}, language = {en} } @article{JesenbergerZmajkovicovaCatalanottietal., author = {Jesenberger, Veronika and Zmajkovicova, Katarina and Catalanotti, Federica and Baumgartner, Christian and Reyes, Gloria Ximena and Baccarini, Manuela}, title = {MEK1 is required for PTEN membrane recruitment, AKT regulation, and the maintenance of peripheral tolerance}, series = {Mol. Cell}, volume = {2013}, journal = {Mol. Cell}, number = {50}, pages = {43 -- 55}, abstract = {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.}, subject = {MEK1 pathway}, language = {en} } @inproceedings{NebelSaladoManzanoJustetal., author = {Nebel, Sabrina and Salado Manzano, Cristina and Just, Valentin and Leeb, Christine and Jesenberger, Veronika}, title = {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}, series = {Proceedings des Forschungsforum 2017 der {\"o}sterreichischen Fachhochschulen}, booktitle = {Proceedings des Forschungsforum 2017 der {\"o}sterreichischen Fachhochschulen}, subject = {Chondrogenesis}, language = {en} } @misc{NebelSaladoManzanoJustetal., author = {Nebel, Sabrina and Salado Manzano, Cristina and Just, Valentin and Leeb, Christine and Jesenberger, Veronika}, title = {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}, subject = {Chondrogenesis}, language = {en} } @article{CatalanottiReyesJesenbergeretal., author = {Catalanotti, Federica and Reyes, Gloria Ximena and Jesenberger, Veronika and Galabova-Kovacs, Gergana and de Matos Simoes, Ricardo and Carugo, Oliviero and Baccarini, Manuela}, title = {A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal}, series = {Nat Struct Mol Biol.}, volume = {2009}, journal = {Nat Struct Mol Biol.}, number = {16(3)}, pages = {294 -- 303}, abstract = {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.}, subject = {Mek1-Mek2 pathway}, language = {en} } @article{KrautwaldBuescherJesenbergeretal., author = {Krautwald, Stefan and B{\"u}scher, Dirk and Jesenberger, Veronika and Buder, Sylke and Baccarini, Manuela}, title = {Involvement of the protein tyrosine phosphatase SHP-1 in Ras-mediated activation of the mitogen-activated protein kinase pathway.}, series = {Mol Cell Biol.}, volume = {1996}, journal = {Mol Cell Biol.}, number = {16(11)}, doi = {doi: 10.1128/mcb.16.11.5955}, pages = {5955 -- 5963}, abstract = {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.}, subject = {Molecular Cell Biology}, language = {en} } @article{JesenbergerProcykYuanetal., author = {Jesenberger, Veronika and Procyk, Katarzyna and Yuan, Junying and Reipert, Siegfried and Baccarini, Manuela}, title = {Salmonella-induced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis}, series = {J Exp Med.}, volume = {2000}, journal = {J Exp Med.}, number = {192(7)}, doi = {10.1084/jem.192.7.1035}, pages = {1035 -- 1046}, abstract = {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.}, subject = {caspase-2 activation in macrophages}, language = {en} } @article{JesenbergerProcykRuethetal., author = {Jesenberger, Veronika and Procyk, Katarzyna and R{\"u}th, Jochen and Schreiber, Martin and Theussl, Hans Christian and Wagner, Erwin and Baccarini, Manuela}, title = {Protective Role of Raf-1 in Salmonella-Induced Macrophage Apoptosis}, series = {J Exp Med.}, volume = {2001}, journal = {J Exp Med.}, number = {193(3)}, doi = {10.1084/jem.193.3.353}, pages = {353 -- 364}, abstract = {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.}, subject = {Salmonella-Induced Macrophage Apoptosis}, language = {en} } @article{JesenbergerJentsch, author = {Jesenberger, Veronika and Jentsch, Stefan}, title = {Deadly encounter: ubiquitin meets apoptosis}, series = {Nat Rev Mol Cell Biol.}, volume = {2002}, journal = {Nat Rev Mol Cell Biol.}, number = {3(2)}, doi = {https://doi.org/10.1038/nrm731}, pages = {112 -- 121}, abstract = {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.}, subject = {programmed cell death}, language = {en} }