Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1
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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 2024
|
| In: |
Aging cell
Year: 2024, Volume: 23, Issue: 5, Pages: 1-16 |
| ISSN: | 1474-9726 |
| DOI: | 10.1111/acel.14128 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1111/acel.14128 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.14128 
|
| Author Notes: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1897491395 | ||
| 003 | DE-627 | ||
| 005 | 20241205155918.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240802s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/acel.14128 |2 doi | |
| 035 | |a (DE-627)1897491395 | ||
| 035 | |a (DE-599)KXP1897491395 | ||
| 035 | |a (OCoLC)1475305407 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Galka, Dajana |e VerfasserIn |0 (DE-588)1337669075 |0 (DE-627)1897491700 |4 aut | |
| 245 | 1 | 0 | |a Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1 |c 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 |
| 246 | 3 | 0 | |a fourteen, one |
| 246 | 3 | 3 | |a Inhibition of 26S proteasome activity by alpha-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1 |
| 264 | 1 | |c May 2024 | |
| 300 | |b Illustrationen | ||
| 300 | |a 16 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Zuerst veröffentlicht: 28. Februar 2024 | ||
| 500 | |a Gesehen am 02.08.2024 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a 26S proteasome | |
| 650 | 4 | |a Parkinson's disease | |
| 650 | 4 | |a posttranslational modifications | |
| 650 | 4 | |a proteasomal chaperone | |
| 650 | 4 | |a protein homeostasis | |
| 650 | 4 | |a tandem fluorescent protein timer | |
| 650 | 4 | |a yeast | |
| 650 | 4 | |a α-Synuclein | |
| 700 | 1 | |a Ali, Tariq T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bast, Alexander |e VerfasserIn |4 aut | |
| 700 | 1 | |a Niederleithinger, Marie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gerhardt, Ellen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Motosugi, Ryo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sakata, Eri |e VerfasserIn |4 aut | |
| 700 | 1 | |a Knop, Michael |e VerfasserIn |0 (DE-588)1064187552 |0 (DE-627)813076749 |0 (DE-576)423832107 |4 aut | |
| 700 | 1 | |a Outeiro, Tiago F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Popova, Blagovesta |e VerfasserIn |4 aut | |
| 700 | 1 | |a Braus, Gerhard H. |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Aging cell |d Oxford [u.a.] : Wiley-Blackwell, 2002 |g 23(2024), 5 vom: Mai, Artikel-ID e14128, Seite 1-16 |h Online-Ressource |w (DE-627)360028705 |w (DE-600)2099130-7 |w (DE-576)103373799 |x 1474-9726 |7 nnas |a Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1 |
| 773 | 1 | 8 | |g volume:23 |g year:2024 |g number:5 |g month:05 |g elocationid:e14128 |g pages:1-16 |g extent:16 |a Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1 |
| 856 | 4 | 0 | |u https://doi.org/10.1111/acel.14128 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.14128 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240802 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 1064187552 |a Knop, Michael |m 1064187552:Knop, Michael |d 700000 |d 706000 |e 700000PK1064187552 |e 706000PK1064187552 |k 0/700000/ |k 1/700000/706000/ |p 8 | ||
| 999 | |a KXP-PPN1897491395 |e 4562018828 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"bibl":"article-journal","media":"Online-Ressource"},"language":["eng"],"id":{"doi":["10.1111/acel.14128"],"eki":["1897491395"]},"relHost":[{"part":{"volume":"23","text":"23(2024), 5 vom: Mai, Artikel-ID e14128, Seite 1-16","pages":"1-16","extent":"16","year":"2024","issue":"5"},"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title_sort":"Aging cell","title":"Aging cell"}],"id":{"issn":["1474-9726"],"zdb":["2099130-7"],"doi":["10.1111/(ISSN)1474-9726"],"eki":["360028705"]},"type":{"bibl":"periodical","media":"Online-Ressource"},"language":["eng"],"origin":[{"publisherPlace":"Oxford [u.a.] ; Oxford [u.a.]","dateIssuedDisp":"2002-","dateIssuedKey":"2002","publisher":"Wiley-Blackwell ; Blackwell"}],"note":["Gesehen am 25.03.22"],"pubHistory":["1.2002 -"],"recId":"360028705","disp":"Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1Aging cell"}],"origin":[{"dateIssuedKey":"2024","dateIssuedDisp":"May 2024"}],"title":[{"title_sort":"Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1","title":"Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1"}],"person":[{"role":"aut","family":"Galka","display":"Galka, Dajana","given":"Dajana"},{"display":"Ali, Tariq T.","family":"Ali","given":"Tariq T.","role":"aut"},{"role":"aut","family":"Bast","display":"Bast, Alexander","given":"Alexander"},{"role":"aut","display":"Niederleithinger, Marie","family":"Niederleithinger","given":"Marie"},{"display":"Gerhardt, Ellen","family":"Gerhardt","given":"Ellen","role":"aut"},{"role":"aut","display":"Motosugi, Ryo","family":"Motosugi","given":"Ryo"},{"role":"aut","family":"Sakata","display":"Sakata, Eri","given":"Eri"},{"role":"aut","display":"Knop, Michael","family":"Knop","given":"Michael"},{"given":"Tiago F.","display":"Outeiro, Tiago F.","family":"Outeiro","role":"aut"},{"display":"Popova, Blagovesta","family":"Popova","given":"Blagovesta","role":"aut"},{"role":"aut","given":"Gerhard H.","family":"Braus","display":"Braus, Gerhard H."}],"titleAlt":[{"title":"Inhibition of 26S proteasome activity by alpha-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1"}],"physDesc":[{"extent":"16 S.","noteIll":"Illustrationen"}],"name":{"displayForm":["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"]},"recId":"1897491395","note":["Zuerst veröffentlicht: 28. Februar 2024","Gesehen am 02.08.2024"]} | ||
| SRT | |a GALKADAJANINHIBITION2024 | ||