Sroka, Kamila

[["dc.bibliographiccitation.firstpage","312"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","321"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Ganesan, S."],["dc.contributor.author","Rohde, G."],["dc.contributor.author","Eckermann, K."],["dc.contributor.author","Sroka, K."],["dc.contributor.author","Schaefer, M. K. E."],["dc.contributor.author","Dohm, C. P."],["dc.contributor.author","Kermer, P."],["dc.contributor.author","Haase, G."],["dc.contributor.author","Wouters, F."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Weishaupt, J. H."],["dc.date.accessioned","2017-09-07T11:48:47Z"],["dc.date.available","2017-09-07T11:48:47Z"],["dc.date.issued","2008"],["dc.description.abstract","Mutant superoxide dismutase 1 (mtSOD1) causes dominantly inherited amyotrophic lateral sclerosis (ALS). The mechanism for mtSOD1 toxicity remains unknown. Two main hypotheses are the impairment of proteasomal function and chaperone depletion by misfolded mtSOD1. Here, we employed FRET/FLIM and biosensor imaging to quantitatively localize ubiquitination, as well as chaperone binding of mtSOD1, and to assess their effect on proteasomal and protein folding activities. We found large differences in ubiquitination and chaperone interaction levels for wild-type (wt) SOD1 versus mtSOD1 in intact single cells. Moreover, SOD1 ubiquitination levels differ between proteasomal structures and cytoplasmic material. Hsp70 binding and ubiquitination of wt and mtSOD1 species are highly correlated, demonstrating the coupled upregulation of both cellular detoxification mechanisms upon mtSOD1 expression. Biosensor imaging in single cells revealed that mtSOD1 expression alters cellular protein folding activity but not proteasomal function in the neuronal cell line examined. Our results provide the first cell-bycell- analysis of SOD1 ubiquitination and chaperone interaction. Moreover, our study opens new methodological avenues for cell biological research on ALS."],["dc.identifier.doi","10.1038/sj.cdd.4402262"],["dc.identifier.gro","3143350"],["dc.identifier.isi","000252387900011"],["dc.identifier.pmid","17992192"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/854"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1350-9047"],["dc.title","Mutant SOD1 detoxification mechanisms in intact single cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","801"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","807"],["dc.bibliographiccitation.volume","111"],["dc.contributor.author","Sroka, Kamila"],["dc.contributor.author","Voigt, Aaron"],["dc.contributor.author","Deeg, Sebastian"],["dc.contributor.author","Reed, John C."],["dc.contributor.author","Schulz, Jörg B."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2017-09-07T11:46:46Z"],["dc.date.available","2017-09-07T11:46:46Z"],["dc.date.issued","2009"],["dc.description.abstract","Bcl-2-associated athanogene-1 (BAG1) is a multifunctional protein delivering chaperone-recognized unfolded substrates to the proteasome for degradation. It has been shown to be essential for proper CNS development in vivo, playing a crucial role in neuronal survival and differentiation. With regard to Huntington's disease, a sequestration of BAG1 into inclusion bodies and a neuroprotective effect in double transgenic mice have been reported. Here, we show that BAG1 reduces aggregation and accelerates degradation of mutant huntingtin (htt-mut). Moreover, it reduces nuclear levels of htt-mut. This effect can be overcome by over-expression of seven in absentia homolog 1, an E3 ligase negatively regulated by BAG1 and known to be involved in nuclear import of htt-mut. In vivo, BAG1 proved to be protective in a Drosophila melanogaster Huntington's disease model, preventing photoreceptor cell loss induced by htt-mut. In summary, we present BAG1 as a therapeutic tool modulating key steps in htt toxicity in vitro and ameliorating htt toxicity in vivo."],["dc.identifier.doi","10.1111/j.1471-4159.2009.06363.x"],["dc.identifier.gro","3143030"],["dc.identifier.isi","000270728600016"],["dc.identifier.pmid","19712056"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/499"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: CMPB; High Q foundation; European Commission [MEST-CT-2004-504193]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.title","BAG1 modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","505"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","513"],["dc.bibliographiccitation.volume","188"],["dc.contributor.author","Deeg, Sebastian"],["dc.contributor.author","Gralle, Mathias"],["dc.contributor.author","Sroka, Kamila"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Wouters, Fred Silvester"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2017-09-07T11:46:08Z"],["dc.date.available","2017-09-07T11:46:08Z"],["dc.date.issued","2010"],["dc.description.abstract","Mutations in the gene coding for DJ-1 protein lead to early-onset recessive forms of Parkinson's disease. It is believed that loss of DJ-1 function is causative for disease, although the function of DJ-1 still remains a matter of controversy. We show that DJ-1 is localized in the cytosol and is associated with membranes and organelles in the form of homodimers. The disease-related mutation L166P shifts its subcellular distribution to the nucleus and decreases its ability to dimerize, impairing cell survival. Using an intracellular foldase biosensor, we found that wild-type DJ-1 possesses chaperone activity, which is abolished by the L166P mutation. We observed that this aberrant phenotype can be reversed by the expression of the cochaperone BAG1 (Bcl-2-associated athanogene 1), restoring DJ-1 subcellular distribution, dimer formation, and chaperone activity and ameliorating cell survival."],["dc.identifier.doi","10.1083/jcb.200904103"],["dc.identifier.gro","3142963"],["dc.identifier.isi","000274723800009"],["dc.identifier.pmid","20156966"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6087"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/425"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft (DFG) [EXC171]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0021-9525"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6678"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Molecules"],["dc.bibliographiccitation.lastpage","6687"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Sroka, Kamila"],["dc.contributor.author","Dohm, Christoph Peter"],["dc.contributor.author","Deeg, Sebastian"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2017-09-07T11:45:18Z"],["dc.date.available","2017-09-07T11:45:18Z"],["dc.date.issued","2010"],["dc.description.abstract","Huntington's disease, one of the so-called poly-glutamine diseases, is a dominantly inherited movement disorder characterized by formation of cytosolic and nuclear inclusion bodies and progressive neurodegeneration. Recently, we have shown that Bcl-2-associated athanogene-1 (BAG1), a multifunctional co-chaperone, modulates toxicity, aggregation, degradation and subcellular distribution in vitro and in vivo of the disease-specific mutant huntingtin protein. Aiming at future small molecule-based therapeutical approaches, we further analysed structural demands for these effects employing the C-terminal deletion mutant BAG Delta C. We show that disruption of the BAG domain known to eliminate intracellular heat shock protein 70 (Hsp70) binding and activation also precludes binding of Siah-1 thereby leaving nuclear huntingtin translocation unaffected. At the same time BAG Delta C fails to induce increased proteasomal huntingtin turnover and does not inhibit intracellular huntingtin aggregation, a pre-requisite necessary for prevention of huntingtin toxicity."],["dc.identifier.doi","10.3390/molecules15106678"],["dc.identifier.gro","3142847"],["dc.identifier.isi","000283587400001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6876"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/296"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: CMPB; High Q foundation; European Commission [MEST-CT-2004-504193]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1420-3049"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Modulation of Huntingtin Toxicity by BAG1 is Dependent on an Intact BAG Domain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Deeg, S."],["dc.contributor.author","Kermer, Pawel"],["dc.contributor.author","Sroka, K."],["dc.contributor.author","Wouters, F."],["dc.date.accessioned","2018-11-07T08:33:11Z"],["dc.date.available","2018-11-07T08:33:11Z"],["dc.date.issued","2009"],["dc.format.extent","228"],["dc.identifier.isi","000269823900031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17515"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.conference","6th German Parkinson Congress of the German-Parkinson-Society (DPG)"],["dc.relation.eventlocation","Marburg, GERMANY"],["dc.relation.issn","0300-9564"],["dc.title","BAG1 restores DJ-1 chaperone function and dimerisation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]