ER stress causes widespread protein aggregation and prion formation

Norfadilah Hamdan, Paraskevi Kritsiligkou, Christopher Grant

Research output: Contribution to journalArticlepeer-review

Abstract

Disturbances in ER homeostasis create a condition termed ER stress. This activates the unfolded protein response (UPR) which alters the expression of many genes involved in ER quality control. We show here that ER stress causes the aggregation of proteins, most of which are not ER or secretory pathway proteins. Proteomic analysis of the aggregated proteins revealed enrichment for intrinsically aggregation-prone proteins, rather than proteins which are affected in a stress-specific manner. Aggregation does not arise due to overwhelming proteasome-mediated degradation, but appears to arise due to a general disruption of cellular protein homeostasis. We further show that overexpression of certain chaperones abrogates protein aggregation and protects a UPR mutant against ER stress conditions. The onset of ER stress is known to correlate with various disease processes and our data indicate that widespread amorphous and amyloid protein aggregation is an unanticipated outcome of such stress.
Original languageEnglish
Pages (from-to)2295–2304
JournalThe Journal of cell biology
Volume216
Issue number8
DOIs
Publication statusPublished - 19 Jun 2017

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