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Keywords = huntingtin protein (Htt), Blm10/PA200-proteasomes

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32 pages, 7416 KiB  
Article
The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin
by Azzam Aladdin, Yanhua Yao, Ciyu Yang, Günther Kahlert, Marvi Ghani, Nikolett Király, Anita Boratkó, Karen Uray, Gunnar Dittmar and Krisztina Tar
Biomolecules 2020, 10(11), 1581; https://doi.org/10.3390/biom10111581 - 20 Nov 2020
Cited by 12 | Viewed by 5435
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, [...] Read more.
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’s disease (HD) research. Full article
(This article belongs to the Special Issue Regulating Proteasome Activity)
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