School of Chemistry - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/300

Filters

2020 - 2022 2
Reset filters

Settings
Statistics
Citations
Author: Nie, Shuai × Author: Reid, Gavin × Author: Cox, Dezerae × Start date: 2020 × End date: 2022 × Type: Journal Article ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    A Census of Hsp70-Mediated Proteome Solubility Changes upon Recovery from Heat Stress
    Sui, X ; Cox, D ; Nie, S ; Reid, GE ; Hatters, DM (AMER CHEMICAL SOC, 2022-05-06)
    Eukaryotic cells respond to heat shock through several regulatory processes including upregulation of stress responsive chaperones and reversible shutdown of cellular activities through formation of protein assemblies. However, the underlying regulatory mechanisms of the recovery of these heat-induced protein assemblies remain largely elusive. Here, we measured the proteome abundance and solubility changes during recovery from heat shock in the mouse Neuro2a cell line. We found that prefoldins and translation machinery are rapidly down-regulated as the first step in the heat shock response. Analysis of proteome solubility reveals that a rapid mobilization of protein quality control machineries, along with changes in cellular energy metabolism, translational activity, and actin cytoskeleton are fundamental to the early stress responses. In contrast, longer term adaptation to stress involves renewal of core cellular components. Inhibition of the Hsp70 family, pivotal for the heat shock response, selectively and negatively affects the ribosomal machinery and delays the solubility recovery of many nuclear proteins. ProteomeXchange: PXD030069.
  • Item
    No Preview Available
    Widespread remodeling of proteome solubility in response to different protein homeostasis stresses
    Sui, X ; Pires, DEV ; Ormsby, AR ; Cox, D ; Nie, S ; Vecchi, G ; Vendruscolo, M ; Ascher, DB ; Reid, GE ; Hatters, DM (National Academy of Sciences, 2020-02-04)
    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 (ΔG). Instead, distinct cellular mechanisms regulate assembly patterns of multiple classes of protein complexes under different stress conditions.