The proteasome activators Blm10/PA200 enhance the proteasomal degradation of N-terminal huntingtin Journal Article
| Authors: | Aladdin, A.; Yao, Y.; Yang, C.; Kahlert, G.; Ghani, M.; Király, N.; Boratkó, A.; Uray, K.; Dittmar, G.; Tar, K. |
| Article 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’s disease (HD) research. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | controlled study; unclassified drug; human cell; gene deletion; nonhuman; mass spectrometry; phenotype; cell viability; proteasome; image analysis; protein degradation; protein protein interaction; protein; immunofluorescence; enzyme activity; genetic transfection; neuroblastoma; saccharomyces cerevisiae; densitometry; western blotting; immunoprecipitation; plasmid; immunoblotting; gene silencing; yeast; centrifugation; penicillin derivative; proteinase inhibitor; sodium chloride; chymotrypsin; glutamine; glutathione; rna extraction; polyacrylamide gel electrophoresis; immunoaffinity chromatography; degradation; streptomycin; protein aggregation; pyruvate sodium; huntington chorea; galactose; buffer; puromycin; deoxyribonuclease i; sepharose; lipofectamine; human; article; confocal laser scanning microscopy; raffinose; formic acid; mercaptoethanol; chemiluminescence immunoassay; pyroxylin; triton x 100; calcium chloride; huntingtin protein (htt), blm10/pa200-proteasomes; huntington’s disease; mutant n-htt aggregates; soluble n-htt; benzamidine; blm10 protein; bromophenol blue; cellulose acetate; odyssey; yeast extract; yeast peptone dextrose; sh-sy5y cell line |
| Journal Title: | Biomolecules |
| Volume: | 10 |
| Issue: | 11 |
| ISSN: | 2218-273X |
| Publisher: | MDPI |
| Date Published: | 2020-11-01 |
| Start Page: | 1581 |
| Language: | English |
| DOI: | 10.3390/biom10111581 |
| PUBMED: | 33233776 |
| PROVIDER: | scopus |
| PMCID: | PMC7699873 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
