{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:55:04Z","timestamp":1789073704753,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009232","name":"Debreceni Egyetem","doi-asserted-by":"publisher","award":["1G3D BKJ0 BFTK 247, 1G3D BK00 BMCK 247"],"award-info":[{"award-number":["1G3D BKJ0 BFTK 247, 1G3D BK00 BMCK 247"]}],"id":[{"id":"10.13039\/501100009232","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013948","name":"Tempus K\u00f6zalap\u00edtv\u00e1ny","doi-asserted-by":"publisher","award":["1Q4D BKX5 STIP 320"],"award-info":[{"award-number":["1Q4D BKX5 STIP 320"]}],"id":[{"id":"10.13039\/501100013948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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\u2019s disease (HD) research.<\/jats:p>","DOI":"10.3390\/biom10111581","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T09:46:18Z","timestamp":1605865578000},"page":"1581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Proteasome Activators Blm10\/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5666-8585","authenticated-orcid":false,"given":"Azzam","family":"Aladdin","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China"},{"name":"Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10460, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10460, USA"},{"name":"Departments of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3969-9547","authenticated-orcid":false,"given":"G\u00fcnther","family":"Kahlert","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvi","family":"Ghani","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolett","family":"Kir\u00e1ly","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Boratk\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6997-459X","authenticated-orcid":false,"given":"Karen","family":"Uray","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3647-8623","authenticated-orcid":false,"given":"Gunnar","family":"Dittmar","sequence":"additional","affiliation":[{"name":"Proteomics of Cellular Signalling, Luxembourg Institute of Health, 1445 Strassen, Luxembourg"},{"name":"Department of Life Science and Medicine, University of Luxembourg, 4365 Esch-sur-Alzette, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1810-0128","authenticated-orcid":false,"given":"Krisztina","family":"Tar","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10460, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1038\/emm.2014.117","article-title":"Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies","volume":"47","author":"Ciechanover","year":"2015","journal-title":"Exp. 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