Targeted protein destabilization reveals an estrogen-mediated ER stress response.

Abstract:

:Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells leads to an unfolded protein response (UPR) that either restores homeostasis or commits the cells to apoptosis. Tools traditionally used to study the UPR are proapoptotic and thus confound analysis of long-term cellular responses to ER stress. Here, we describe an ER-localized HaloTag (ERHT) protein that can be conditionally destabilized using a small-molecule hydrophobic tag (HyT36). Treatment of ERHT-expressing cells with HyT36 induces acute, resolvable ER stress that results in transient UPR activation without induction of apoptosis. Transcriptome analysis of late-stage responses to this UPR stimulus reveals a link between UPR activity and estrogen signaling.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Raina K,Noblin DJ,Serebrenik YV,Adams A,Zhao C,Crews CM

doi

10.1038/nchembio.1638

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

957-62

issue

11

eissn

1552-4450

issn

1552-4469

pii

nchembio.1638

journal_volume

10

pub_type

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