Wienken, Magdalena

[["dc.bibliographiccitation.artnumber","5470831"],["dc.bibliographiccitation.journal","Mediators of Inflammation"],["dc.contributor.author","Schmidt, Karsten"],["dc.contributor.author","Wienken, Magdalena"],["dc.contributor.author","Keller, Christian W."],["dc.contributor.author","Balcarek, Peter"],["dc.contributor.author","Münz, Christian"],["dc.contributor.author","Schmidt, Jens"],["dc.date.accessioned","2018-11-07T10:29:09Z"],["dc.date.available","2018-11-07T10:29:09Z"],["dc.date.issued","2017"],["dc.description.abstract","The pathology of inclusion body myositis (IBM) involves an inflammatory response and beta-amyloid deposits in muscle fibres. It is believed that MAP kinases such as the ERK signalling pathway mediate the inflammatory signalling in cells. Further, there is evidence that autophagic activity plays a crucial role in the pathogenesis of IBM. Using a well established in vitro model of IBM, the autophagic pathway, MAP kinases, and accumulation of beta-amyloid were examined. We demonstrate that stimulation of muscle cells with IL-1 beta and IFN-gamma led to an increased phosphorylation of ERK. The ERK inhibitor PD98059 diminished the expression of proinflammatory markers as well as the accumulation of beta-amyloid. In addition, IL-1 beta and IFN-gamma led to an increase of autophagic activity, upregulation of APP, and subsequent accumulation of beta-sheet aggregates. Taken together, the data demonstrate that the ERK pathway contributes to formation of beta-amyloid and regulation of autophagic activity in muscle cells exposed to proinflammatory cell stress. This suggests that ERK serves as an important mediator between inflammatory mechanisms and protein deposition in skeletal muscle and is a crucial element of the pathology of IBM."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1155/2017/5470831"],["dc.identifier.isi","000394098400001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14140"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43582"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Hindawi Ltd"],["dc.relation.issn","1466-1861"],["dc.relation.issn","0962-9351"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","IL-1 beta-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1845"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","1857"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Klusmann, Ina"],["dc.contributor.author","Rodewald, Sabrina"],["dc.contributor.author","Mueller, Leonie"],["dc.contributor.author","Friedrich, Mascha"],["dc.contributor.author","Wienken, Magdalena"],["dc.contributor.author","Li, Yizhu"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2018-11-07T10:05:50Z"],["dc.date.available","2018-11-07T10:05:50Z"],["dc.date.issued","2016"],["dc.description.abstract","p53 induces cell death upon DNA damage, but this may not confer all of its tumor suppressor activity. Wereport that p53 activation enhances the processivity of DNA replication, as monitored by multi-label fiber assays, whereas removal of p53 reduces fork progression. This is observed in tumor-derived U2OS cells but also in murine embryonic fibroblasts with heterozygous or homozygous p53 deletion and in freshly isolated thymocytes frommice with differential p53 status. Mdm2, a p53-inducible gene product, similarly supports DNA replication even in p53-deficient cells, suggesting that sustained Mdm2-expression is at least one of the mechanisms allowing p53 to prevent replicative stress. Thus, p53 helps to protect the genome during S phase, by preventing the occurrence of stalled or collapsed replication forks. These results expand p53's tumor-suppressive functions, adding to the ex-post model (elimination of damaged cells) an ex-ante activity; i.e., the prevention of DNA damage during replication."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1016/j.celrep.2016.10.036"],["dc.identifier.isi","000390545900014"],["dc.identifier.pmid","27829155"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14102"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38979"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","2211-1247"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","p53 Activity Results in DNA Replication Fork Processivity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","31623"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","31638"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Sriraman, Anusha"],["dc.contributor.author","Radovanovic, Marija"],["dc.contributor.author","Wienken, Magdalena"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Li, Yizhu"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2018-11-07T10:14:02Z"],["dc.date.available","2018-11-07T10:14:02Z"],["dc.date.issued","2016"],["dc.description.abstract","Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e.g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1-depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists."],["dc.identifier.doi","10.18632/oncotarget.9302"],["dc.identifier.isi","000377748500002"],["dc.identifier.pmid","27183917"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14134"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40550"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]