Journal article

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

Xiaojing Sui, Douglas EV Pires, Angelique R Ormsby, Dezerae Cox, Shuai Nie, Giulia Vecchi, Michele Vendruscolo, David B Ascher, Gavin E Reid, Danny M Hatters

Proceedings of the National Academy of Sciences of the United States of America | National Academy of Sciences | Published : 2020


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 str..

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