| Author | Sui, Xiaojing | |
| Author | Pires, Douglas Eduardo Valente | |
| Author | Ormsby, Angelique R | |
| Author | Cox, Dezerae | |
| Author | Nie, Shuai | |
| Author | Vecchi, Giulia | |
| Author | Vendruscolo, Michele | |
| Author | Ascher, David B | |
| Author | Reid, Gavin E | |
| Author | Hatters, Danny M | |
| Access date | 2023-05-18T15:35:02Z | |
| Available date | 2023-05-18T15:35:02Z | |
| Document date | 2020 | |
| Citation | SUI, Xiaojing et al. Widespread remodeling of proteome solubility in response to different protein homeostasis stresses. Proc Natl Acad Sci U S A, v. 117, n. 5, p. 2422-2431, 2020. doi: 10.1073/pnas.1912897117. | en_US |
| ISSN | 0027-8424 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/58478 | |
| Language | eng | en_US |
| Publisher | National Academy of Sciences | en_US |
| Rights | restricted access | |
| Title | Widespread remodeling of proteome solubility in response to different protein homeostasis stresses | en_US |
| Type | Article | |
| DOI | 10.1073/pnas.1912897117 | |
| Abstract | The accumulation of protein deposits in neurodegenerative diseases has been hypothesized to depend on a metastable subproteome vulnerable to aggregation. To investigate this phenomenon and the mechanisms that regulate it, we measured the solubility of the proteome in the mouse Neuro2a cell line under six different protein homeostasis stresses: 1) Huntington's disease proteotoxicity, 2) Hsp70, 3) Hsp90, 4) proteasome, 5) endoplasmic reticulum (ER)-mediated folding inhibition, and 6) oxidative stress. Overall, we found that about one-fifth of the proteome changed solubility with almost all of the increases in insolubility were counteracted by increases in solubility of other proteins. Each stress directed a highly specific pattern of change, which reflected the remodeling of protein complexes involved in adaptation to perturbation, most notably, stress granule (SG) proteins, which responded differently to different stresses. These results indicate that the protein homeostasis system is organized in a modular manner and aggregation patterns were not correlated with protein folding stability (AG). Instead, distinct cellular mechanisms regulate assembly patterns of multiple classes of protein complexes under different stress conditions. | en_US |
| Affilliation | Department of Biochemistry and Molecular Biology. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia | en_US |
| Affilliation | Department of Biochemistry and Molecular Biology. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia/Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/School of Computing and Information Systems. The University of Melbourne. VIC 3010, Australia. | en_US |
| Affilliation | Department of Biochemistry and Molecular Biology. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia. | en_US |
| Affilliation | Department of Biochemistry and Molecular Biology. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia. | en_US |
| Affilliation | Melbourne Mass Spectrometry and Proteomics Facility. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia. | en_US |
| Affilliation | Department of Chemistry. Centre for Misfolding Diseases. University of Cambridge. Cambridge, United Kingdom. | en_US |
| Affilliation | Department of Chemistry. Centre for Misfolding Diseases. University of Cambridge. Cambridge, United Kingdom. | en_US |
| Affilliation | Department of Biochemistry and Molecular Biology. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia. | en_US |
| Affilliation | Department of Biochemistry and Molecular Biology. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia/School of Chemistry. The University of Melbourne. VIC 3010, Australia. | en_US |
| Affilliation | Department of Biochemistry and Molecular Biology. Bio21 Molecular Science and Biotechnology Institute. The University of Melbourne. VIC 3010, Australia | en_US |
| Subject | Huntington's disease | en_US |
| Subject | molecular chaperones | en_US |
| Subject | protein aggregation | en_US |
| Subject | protein homeostasis | en_US |
| Subject | protein misfolding | en_US |
| Embargo date | 2040-12-31 | |
