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Status: Bibliographieeintrag

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Verfasst von:Galka, Dajana [VerfasserIn]   i
 Ali, Tariq T. [VerfasserIn]   i
 Bast, Alexander [VerfasserIn]   i
 Niederleithinger, Marie [VerfasserIn]   i
 Gerhardt, Ellen [VerfasserIn]   i
 Motosugi, Ryo [VerfasserIn]   i
 Sakata, Eri [VerfasserIn]   i
 Knop, Michael [VerfasserIn]   i
 Outeiro, Tiago F. [VerfasserIn]   i
 Popova, Blagovesta [VerfasserIn]   i
 Braus, Gerhard H. [VerfasserIn]   i
Titel:Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1
Verf.angabe:Dajana Galka, Tariq T. Ali, Alexander Bast, Marie Niederleithinger, Ellen Gerhardt, Ryo Motosugi, Eri Sakata, Michael Knop, Tiago F. Outeiro, Blagovesta Popova, Gerhard H. Braus
E-Jahr:2024
Jahr:May 2024
Umfang:16 S.
Illustrationen:Illustrationen
Fussnoten:Zuerst veröffentlicht: 28. Februar 2024 ; Gesehen am 02.08.2024
Titel Quelle:Enthalten in: Aging cell
Ort Quelle:Oxford [u.a.] : Wiley-Blackwell, 2002
Jahr Quelle:2024
Band/Heft Quelle:23(2024), 5 vom: Mai, Artikel-ID e14128, Seite 1-16
ISSN Quelle:1474-9726
Abstract:Parkinson's disease (PD) is characterized by aggregation of α-synuclein (α-syn) into protein inclusions in degenerating brains. Increasing amounts of aggregated α-syn species indicate significant perturbation of cellular proteostasis. Altered proteostasis depends on α-syn protein levels and the impact of α-syn on other components of the proteostasis network. Budding yeast Saccharomyces cerevisiae was used as eukaryotic reference organism to study the consequences of α-syn expression on protein dynamics. To address this, we investigated the impact of overexpression of α-syn and S129A variant on the abundance and stability of most yeast proteins using a genome-wide yeast library and a tandem fluorescent protein timer (tFT) reporter as a measure for protein stability. This revealed that the stability of in total 377 cellular proteins was altered by α-syn expression, and that the impact on protein stability was significantly enhanced by phosphorylation at Ser129 (pS129). The proteasome assembly chaperone Rpn14 was identified as one of the top candidates for increased protein stability by expression of pS129 α-syn. Elevated levels of Rpn14 enhanced the growth inhibition by α-syn and the accumulation of ubiquitin conjugates in the cell. We found that Rpn14 interacts physically with α-syn and stabilizes pS129 α-syn. The expression of α-syn along with elevated levels of Rpn14 or its human counterpart PAAF1 reduced the proteasome activity in yeast and in human cells, supporting that pS129 α-syn negatively affects the 26S proteasome through Rpn14. This comprehensive study into the alternations of protein homeostasis highlights the critical role of the Rpn14/PAAF1 in α-syn-mediated proteasome dysfunction.
DOI:doi:10.1111/acel.14128
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1111/acel.14128
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.14128
 DOI: https://doi.org/10.1111/acel.14128
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:26S proteasome
 Parkinson's disease
 posttranslational modifications
 proteasomal chaperone
 protein homeostasis
 tandem fluorescent protein timer
 yeast
 α-Synuclein
K10plus-PPN:1897491395
Verknüpfungen:→ Zeitschrift

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