Abstract
Protein aggregates and nuclear inclusions (NIs) containing components of the ubiquitin-proteasome system (UPS), expanded polyglutamine (polyQ) proteins, and transcriptional coactivators characterize cellular responses to stress and are hallmarks of neurodegenerative diseases. The biological function of polyQ-containing aggregates is unknown. To analyze proteasomal activity within such aggregates, we present a nanoparticle (NP)-based method that enables controlled induction of sodium dodecyl sulfate-resistant inclusions of endogenous nuclear proteins while normal regulatory mechanisms remain in place. Consistent with the idea that the UPS maintains quality control, inhibition of proteasomal proteolysis promotes extra large protein aggregates (1.4-2 μm), whereas formation of NP-induced NIs is found to be inversely correlated to proteasome activation. We show that global proteasomal proteolysis increases in NP-treated nuclei and, on the local level, a subpopulation of NIs overlaps with focal domains of proteasome-dependent protein degradation. These results suggest that inclusions in the nucleus constitute active proteolysis modules that may serve to concentrate and decompose damaged, malfolded, or misplaced proteins. © The Rockefeller University Press.
Recommended Citation
M. Chen et al., "Nuclear Polyglutamine-containing Protein Aggregates As Active Proteolytic Centers," Journal of Cell Biology, vol. 180, no. 4, pp. 697 - 704, Rockefeller University Press, Feb 2008.
The definitive version is available at https://doi.org/10.1083/jcb.200708131
Department(s)
Biological Sciences
International Standard Serial Number (ISSN)
0021-9525; 0021-9525
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2023 The Authors, All rights reserved.
Publication Date
25 Feb 2008
PubMed ID
18283109
