Popova, Blagovesta

[["dc.bibliographiccitation.firstpage","27567"],["dc.bibliographiccitation.issue","33"],["dc.bibliographiccitation.journal","The Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","27579"],["dc.bibliographiccitation.volume","287"],["dc.contributor.author","Petroi, Doris"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Taheri-Talesh, Naimeh"],["dc.contributor.author","Irniger, Stefan"],["dc.contributor.author","Shahpasandzadeh, Hedieh"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Braus, Gerhard H."],["dc.date.accessioned","2018-09-28T08:45:30Z"],["dc.date.available","2018-09-28T08:45:30Z"],["dc.date.issued","2012"],["dc.description.abstract","Parkinson disease is the second most common neurodegenerative disease. The molecular hallmark is the accumulation of proteinaceous inclusions termed Lewy bodies containing misfolded and aggregated α-synuclein. The molecular mechanism of clearance of α-synuclein aggregates was addressed using the bakers' yeast Saccharomyces cerevisiae as the model. Overexpression of wild type α-synuclein or the genetic variant A53T integrated into one genomic locus resulted in a gene copy-dependent manner in cytoplasmic proteinaceous inclusions reminiscent of the pathogenesis of the disease. In contrast, overexpression of the genetic variant A30P resulted only in transient aggregation, whereas the designer mutant A30P/A36P/A76P neither caused aggregation nor impaired yeast growth. The α-synuclein accumulation can be cleared after promoter shut-off by a combination of autophagy and vacuolar protein degradation. Whereas the proteasomal inhibitor MG-132 did not significantly inhibit aggregate clearance, treatment with phenylmethylsulfonyl fluoride, an inhibitor of vacuolar proteases, resulted in significant reduction in clearance. Consistently, a cim3-1 yeast mutant restricted in the 19 S proteasome regulatory subunit was unaffected in clearance, whereas an Δatg1 yeast mutant deficient in autophagy showed a delayed aggregate clearance response. A cim3-1Δatg1 double mutant was still able to clear aggregates, suggesting additional cellular mechanisms for α-synuclein clearance. Our data provide insight into the mechanisms yeast cells use for clearing different species of α-synuclein and demonstrate a higher contribution of the autophagy/vacuole than the proteasome system. This contributes to the understanding of how cells can cope with toxic and/or aggregated proteins and may ultimately enable the development of novel strategies for therapeutic intervention."],["dc.identifier.doi","10.1074/jbc.M112.361865"],["dc.identifier.pmid","22722939"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15838"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1083-351X"],["dc.title","Aggregate clearance of α-synuclein in Saccharomyces cerevisiae depends more on autophagosome and vacuole function than on the proteasome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Yeast"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Shahpasandzadeh, Hedieh"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Braus, Gerhard"],["dc.date.accessioned","2018-11-07T09:20:12Z"],["dc.date.available","2018-11-07T09:20:12Z"],["dc.date.issued","2013"],["dc.format.extent","80"],["dc.identifier.isi","000327927400109"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28827"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","26th International Conference on Yeast Genetics and Molecular Biology"],["dc.relation.eventlocation","Frankfurt Main, GERMANY"],["dc.relation.issn","1097-0061"],["dc.relation.issn","0749-503X"],["dc.title","Interplay of post-translational modifications of alpha-synuclein in yeast model of Parkinson disease"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1142"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Eukaryotic Cell"],["dc.bibliographiccitation.lastpage","1154"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Herzog, Britta"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Jakobshagen, Antonia"],["dc.contributor.author","Shahpasandzadeh, Hedieh"],["dc.contributor.author","Braus, Gerhard H."],["dc.date.accessioned","2018-09-28T08:38:51Z"],["dc.date.available","2018-09-28T08:38:51Z"],["dc.date.issued","2013"],["dc.description.abstract","Hac1 is the activator of the cellular response to the accumulation of unfolded proteins in the endoplasmic reticulum. Hac1 function requires the activity of Gcn4, which mainly acts as a regulator of the general amino acid control network providing Saccharomyces cerevisiae cells with amino acids. Here, we demonstrate novel functions of Hac1 and describe a mutual connection between Hac1 and Gcn4. Hac1 is required for induction of Gcn4-responsive promoter elements in haploid as well as diploid cells and therefore participates in the cellular amino acid supply. Furthermore, Hac1 and Gcn4 mutually influence their mRNA expression levels. Hac1 is also involved in FLO11 expression and adhesion upon amino acid starvation. Hac1 and Gcn4 act through the same promoter regions of the FLO11 flocculin. The results indicate an indirect effect of both transcription factors on FLO11 expression. Our data suggest a complex mutual cross talk between the Hac1- and Gcn4-controlled networks."],["dc.identifier.doi","10.1128/EC.00123-13"],["dc.identifier.pmid","23794510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15837"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1535-9786"],["dc.title","Mutual cross talk between the regulators Hac1 of the unfolded protein response and Gcn4 of the general amino acid control of Saccharomyces cerevisiae"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","31224"],["dc.bibliographiccitation.issue","45"],["dc.bibliographiccitation.journal","The Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","31240"],["dc.bibliographiccitation.volume","289"],["dc.contributor.author","Shahpasandzadeh, Hedieh"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Kleinknecht, Alexandra"],["dc.contributor.author","Fraser, Paul E."],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Braus, Gerhard H."],["dc.date.accessioned","2018-09-28T08:29:52Z"],["dc.date.available","2018-09-28T08:29:52Z"],["dc.date.issued","2014"],["dc.description.abstract","Parkinson disease is associated with the progressive loss of dopaminergic neurons from the substantia nigra. The pathological hallmark of the disease is the accumulation of intracytoplasmic inclusions known as Lewy bodies that consist mainly of post-translationally modified forms of α-synuclein. Whereas phosphorylation is one of the major modifications of α-synuclein in Lewy bodies, sumoylation has recently been described. The interplay between α-synuclein phosphorylation and sumoylation is poorly understood. Here, we examined the interplay between these modifications as well as their impact on cell growth and inclusion formation in yeast. We found that α-synuclein is sumoylated in vivo at the same sites in yeast as in human cells. Impaired sumoylation resulted in reduced yeast growth combined with an increased number of cells with inclusions, suggesting that this modification plays a protective role. In addition, inhibition of sumoylation prevented autophagy-mediated aggregate clearance. A defect in α-synuclein sumoylation could be suppressed by serine 129 phosphorylation by the human G protein-coupled receptor kinase 5 (GRK5) in yeast. Phosphorylation reduced foci formation, alleviated yeast growth inhibition, and partially rescued autophagic α-synuclein degradation along with the promotion of proteasomal degradation, resulting in aggregate clearance in the absence of a small ubiquitin-like modifier. These findings suggest a complex interplay between sumoylation and phosphorylation in α-synuclein aggregate clearance, which may open new horizons for the development of therapeutic strategies for Parkinson disease."],["dc.identifier.doi","10.1074/jbc.M114.559237"],["dc.identifier.pmid","25231978"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15835"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1083-351X"],["dc.title","Interplay between sumoylation and phosphorylation for protection against α-synuclein inclusions"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]