Dataset Information

Proteome solubility changes under different proteostasis stresses

ABSTRACT: The accumulation of aberrant protein aggregates in neurodegenerative diseases is associated with a widespread failure of the protein homeostasis system. To investigate whether there is a subproteome that consistently aggregates under stress and define the broader determinants for protein aggregation at the proteome level we measured the changes in proteome solubility of a mouse neuroblastoma cell line (Neuro2a) under 6 different protein homeostasis stresses, including a Huntington’s disease model, Hsp70, Hsp90, proteasome and ER-mediated folding inhibition, and oxidative stress. By partitioning cell lysates into supernatants and pellets by centrifugation, we found that just over a one-quarter of the proteome extensively changed in solubility upon one or more stresses. Surprisingly, almost all the increases in insolubility were counteracted by increases on solubility of other proteins. Each stress directed a highly specific pattern of change, which reflected the remodelling of protein complexes involved in adaptation to perturbation, most notably stress granule proteins, which were highly enriched but responded differently across the different 2 stresses. The solubility patterns clustered into molecular functions anticipated from stress responses and metabolic pathway hotspots, and indicate a robust rewiring of protein-ligand interactions.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Xiaojing Sui

LAB HEAD: Daniel Martin Hatters

PROVIDER: PXD015573 | Pride | 2020-01-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	17-AAG_Pelletproteome_Replicate1.raw	Raw
	17-AAG_Pelletproteome_Replicate2.raw	Raw
	17-AAG_Pelletproteome_Replicate3.raw	Raw
	17-AAG_Pelletproteome_Replicate4.raw	Raw
	17-AAG_Supernatant_Totalproteome_17-AAG_Replicate1.raw	Raw

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Publications

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

Sui Xiaojing X Pires Douglas E V DEV Ormsby Angelique R AR Cox Dezerae D Nie Shuai S Vecchi Giulia G Vendruscolo Michele M Ascher David B DB Reid Gavin E GE Hatters Danny M DM

Proceedings of the National Academy of Sciences of the United States of America 20200121 5

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 str ...[more]

PMID: 31964829

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