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


SUMMARY The accumulation of wide range of different protein deposits in neurodegenerative diseases has been associated with the presence of a metastable subproteome vulnerable to aggregation. To investigate this subproteome and the mechanisms that regulates it, 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 over one-quarter of the proteome extensively changed in solubility upon one or more..

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