Widespread remodeling of proteome solubility in response to different protein homeostasis stresses

dc.creatorSui, Xiaojing
dc.creatorPires, Douglas Eduardo Valente
dc.creatorOrmsby, Angelique R
dc.creatorCox, Dezerae
dc.creatorNie, Shuai
dc.creatorVecchi, Giulia
dc.creatorVendruscolo, Michele
dc.creatorAscher, David B
dc.creatorReid, Gavin E
dc.creatorHatters, Danny M
dc.date2023-05-18T15:35:02Z
dc.date2023-05-18T15:35:02Z
dc.date2020
dc.date.accessioned2023-09-26T20:25:47Z
dc.date.available2023-09-26T20:25:47Z
dc.identifierSUI, 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.
dc.identifier0027-8424
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/58478
dc.identifier10.1073/pnas.1912897117
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8856704
dc.descriptionThe 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.
dc.description2040-12-31
dc.formatapplication/pdf
dc.languageeng
dc.publisherNational Academy of Sciences
dc.rightsrestricted access
dc.subjectHuntington's disease
dc.subjectmolecular chaperones
dc.subjectprotein aggregation
dc.subjectprotein homeostasis
dc.subjectprotein misfolding
dc.titleWidespread remodeling of proteome solubility in response to different protein homeostasis stresses
dc.typeArticle


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