Format

Send to

Choose Destination
Nat Chem Biol. 2014 Nov;10(11):957-62. doi: 10.1038/nchembio.1638. Epub 2014 Sep 21.

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

Author information

1
1] Department of Chemistry, Yale University New Haven, Connecticut, USA. [2].
2
1] Department of Molecular, Cellular and Developmental Biology, Yale University New Haven, Connecticut, USA. [2].
3
Department of Molecular, Cellular and Developmental Biology, Yale University New Haven, Connecticut, USA.
4
Molecular Biophysics and Biochemistry, Yale University New Haven, Connecticut, USA.
5
1] Department of Chemistry, Yale University New Haven, Connecticut, USA. [2] Department of Molecular, Cellular and Developmental Biology, Yale University New Haven, Connecticut, USA. [3] Department of Pharmacology, Yale University New Haven, Connecticut, USA.

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.

PMID:
25242550
PMCID:
PMC4324732
DOI:
10.1038/nchembio.1638
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center