% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Galka:288728,
      author       = {D. Galka and T. T. Ali and A. Bast and M. Niederleithinger
                      and E. Gerhardt and R. Motosugi and E. Sakata and M.
                      Knop$^*$ and T. F. Outeiro and B. Popova and G. H. Braus},
      title        = {{I}nhibition of 26{S} proteasome activity by α-synuclein
                      is mediated by the proteasomal chaperone {R}pn14/{PAAF}1.},
      journal      = {Aging cell},
      volume       = {23},
      number       = {5},
      issn         = {1474-9718},
      address      = {Oxford [u.a.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2024-00437},
      pages        = {e14128},
      year         = {2024},
      note         = {2024 May;23(5):e14128 / DKFZ-ZMBH Alliance},
      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.},
      keywords     = {26S proteasome (Other) / Parkinson's disease (Other) /
                      posttranslational modifications (Other) / proteasomal
                      chaperone (Other) / protein homeostasis (Other) / tandem
                      fluorescent protein timer (Other) / yeast (Other) /
                      α-Synuclein (Other)},
      cin          = {A260},
      ddc          = {610},
      cid          = {I:(DE-He78)A260-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38415292},
      doi          = {10.1111/acel.14128},
      url          = {https://inrepo02.dkfz.de/record/288728},
}