Targeted protein destabilization reveals an estrogen-mediated ER stress response.
Kanak RainaDevin J NoblinYevgeniy V SerebrenikAlison AdamsConnie ZhaoCraig M CrewsPublished in: Nature chemical biology (2014)
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.
Keyphrases
- endoplasmic reticulum
- cell cycle arrest
- induced apoptosis
- endoplasmic reticulum stress
- cell death
- small molecule
- oxidative stress
- protein protein
- pi k akt
- amino acid
- liver failure
- binding protein
- signaling pathway
- cell proliferation
- single cell
- intensive care unit
- dna methylation
- ionic liquid
- combination therapy
- brain injury
- subarachnoid hemorrhage
- smoking cessation
- aortic dissection