Journal article

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

Xiaojing Sui, Douglas Pires, Shuai Nie, Giulia Vecchi, Michele Vendruscolo, David Ascher, Gavin Reid, Danny Hatters

Published : 2019


ABSTRACT The accumulation of protein deposits in neurodegenerative diseases involves the presence of a metastable subproteome vulnerable to aggregation. To investigate this subproteome and the mechanisms that regulates it, we measured the proteome solubility of the Neuro2a cell line under protein homeostasis stresses induced by Huntington Disease proteotoxicity; Hsp70, Hsp90, proteasome and ER-mediated folding inhibition; and oxidative stress. We found one-quarter of the proteome extensively changed solubility. Remarkably, almost all the increases in insolubility were counteracted by increases in solubility of other proteins. Each stress directed a highly specific pattern of change, which re..

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