| http://purl.uniprot.org/citations/15591046 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15591046 | http://www.w3.org/2000/01/rdf-schema#comment | "The accumulation of aggregated alpha-synuclein is thought to contribute to the pathogenesis of Parkinson's disease. Recent studies indicate that aggregated alpha-synuclein binds to S6', a component of the 19 S subunit in the 26 S proteasome and inhibits 26 S proteasomal degradation, both ubiquitin-independent and ubiquitin-dependent. The IC(50) of aggregated alpha-synuclein for inhibition of the 26 S ubiquitin-independent proteasomal activity is approximately 1 nm. alpha-Synuclein has two close homologues, termed beta-synuclein and gamma-synuclein. In the present study we compared the effects of the three synuclein homologues on proteasomal activity. The proteasome exists as a 26 S and a 20 S species, with the 26 S proteasome containing the 20 S core and 19 S cap. Monomeric alpha- and beta-synucleins inhibited the 20 S and 26 S proteasomal activities only weakly, but monomeric gamma-synuclein strongly inhibited ubiquitin-independent proteolysis. The IC(50) of monomeric gamma-synuclein for the 20 S proteolysis was 400 nm. In monomeric form, none of the three synuclein proteins inhibited 26 S ubiquitin-dependent proteasomal activity. Although beta-synuclein had no direct effect on proteasomal activity, co-incubating monomeric beta-synuclein with aggregated alpha-synuclein antagonized the inhibition of the 26 S ubiquitin-independent proteasome by aggregated alpha-synuclein when added before the aggregated alpha-synuclein. Co-incubating beta-synuclein with gamma-synuclein had no effect on the inhibition of the 20 S proteasome by monomeric gamma-synuclein. Immunoprecipitation and pull-down experiments suggested that antagonism by beta-synuclein resulted from binding to alpha-synuclein rather than binding to S6'. Pull-down experiments demonstrated that recombinant monomeric beta-synuclein does not interact with the proteasomal subunit S6', unlike alpha-synuclein, but beta-synuclein does bind alpha-synuclein and competes with S6' for binding to alpha-synuclein. Based on these data, we hypothesize that the alpha- and gamma-synucleins regulate proteasomal function and that beta-synuclein acts as a negative regulator of alpha-synuclein."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m412887200"xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Hashimoto M."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Masliah E."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Hsu C."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Snyder H."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Surguchov A."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Matouschek A."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Surgucheva I.G."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Wolozin B."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Mensah K."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/author | "Festoff B."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/pages | "7562-7569"xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/title | "beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein."xsd:string |
| http://purl.uniprot.org/citations/15591046 | http://purl.uniprot.org/core/volume | "280"xsd:string |
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| http://purl.uniprot.org/citations/15591046 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15591046 |
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| http://purl.uniprot.org/uniprot/#_H6UYS0-mappedCitation-15591046 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15591046 |