@article{7d947e25583547dc87174c85e9cad091,
title = "The proteasome activators Blm10/PA200 enhance the proteasomal degradation of N-terminal huntingtin",
abstract = "The Blm10/PA200 family of proteasome activators modulates the peptidase activity of the core particle (20S CP). They participate in opening the 20S CP gate, thus facilitating the degradation of unstructured proteins such as tau and Dnm1 in a ubiquitin-and ATP-independent manner. Furthermore, PA200 also participates in the degradation of acetylated histones. In our study, we use a combination of yeast and human cell systems to investigate the role of Blm10/PA200 in the degradation of N-terminal Huntingtin fragments (N-Htt). We demonstrate that the human PA200 binds to N-Htt. The loss of Blm10 in yeast or PA200 in human cells results in increased mutant N-Htt aggregate formation and elevated cellular toxicity. Furthermore, Blm10 in vitro accelerates the proteasomal degradation of soluble N-Htt. Collectively, our data suggest N-Htt as a new substrate for Blm10/PA200-proteasomes and point to new approaches in Huntington{\textquoteright}s disease (HD) research.",
keywords = "Degradation, Huntingtin protein (Htt), Blm10/PA200-proteasomes, Huntington{\textquoteright}s disease, Mutant N-Htt aggregates, Soluble N-Htt",
author = "Azzam Aladdin and Yanhua Yao and Ciyu Yang and G{\"u}nther Kahlert and Marvi Ghani and Nikolett Kir{\'a}ly and Anita Boratk{\'o} and Karen Uray and Gunnar Dittmar and Krisztina Tar",
note = "Funding Information: Acknowledgments: We would like to thank Marion Schmidt (Albert Einstein College of Medicine, Department of Biochemistry), who was supported by NIH R01 GM084228. We appreciate the technical assistance of Andrea Tank{\'a}n{\'e} Farkas, Mih{\'a}lyn{\'e} Herb{\'a}ly, Erika Guly{\'a}s, and D{\'a}vid Varga. K.T. received a Lajos Szodoray Fellowship from the University of Debrecen. Funding Information: Funding: This study was supported by the University of Debrecen, Debrecen, Hungary by a Bridging Fund, by a fund from the International Education Office, University of Debrecen, Debrecen, Hungary for the corresponding author and by the Tempus Foundation, Stipendium Hungaricum for A.A. and K.T. Y.Y. also received funding from the National Natural Science Foundation of China (81901284) and Shanghai Science and Technology (18ZR1421700). Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = nov,
doi = "10.3390/biom10111581",
language = "English",
volume = "10",
pages = "1--32",
journal = "Biomolecules",
issn = "2218-273X",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "11",
}