ArticlePloS one2012
Intracellular context affects levels of a chemically dependent destabilizing domain.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Engineering Protein Stability with Small Molecules: A Review of the ecDHFR Destabilizing Domain System.ACS chemical biology · 2026Review
- Utility of the DHFR-based destabilizing domain across mouse models of retinal degeneration and aging.iScience · 2022Article
- Endogenous ROS production in early differentiation state suppresses endoderm differentiation via transient FOXC1 expression.Cell death discovery · 2022Article
- Protocol forSTAR protocols · 2020Article
- Protocol for Designing Small-Molecule-Regulated Destabilizing Domains forSTAR protocols · 2020Article
- A technique for delineating the unfolding requirements for substrate entry into retrotranslocons during endoplasmic reticulum-associated degradation.The Journal of biological chemistry · 2019Article
- Development of a conditional localization approach to control apicoplast protein trafficking in malaria parasites.Traffic (Copenhagen, Denmark) · 2019Article
- Small-molecule-based regulation of RNA-delivered circuits in mammalian cells.Nature chemical biology · 2018Article
- A Drug-Tunable Gene Therapy for Broad-Spectrum Protection against Retinal Degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- A Destabilizing Domain Allows for Fast, Noninvasive, Conditional Control of Protein Abundance in the Mouse Eye - Implications for Ocular Gene Therapy.Investigative ophthalmology & visual science · 2018Article
- An optimized, broadly applicable piggyBac transposon induction system.Nucleic acids research · 2017Article
- CRISPR/Cas9-based tools for targeted genome editing and replication control of HBV.Virologica Sinica · 2015Review
- The therapeutic application of CRISPR/Cas9 technologies for HIV.Expert opinion on biological therapy · 2015Review
- Targeted protein destabilization reveals an estrogen-mediated ER stress response.Nature chemical biology · 2014Article
- Chemical biology strategies for posttranslational control of protein function.Chemistry & biology · 2014Review
- Imaging of nuclear factor κB activation induced by ionizing radiation in human embryonic kidney (HEK) cells.Radiation and environmental biophysics · 2014Article
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- Functional neuroprotection and efficient regulation of GDNF using destabilizing domains in a rodent model of Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The ability to regulate protein levels in live cells is crucial to understanding protein function. In the interest of advancing the tool set for protein perturbation, we developed a protein destabilizing domain (DD) that can confer its instability to a fused protein of interest. This destabilization and consequent degradation can be rescued in a reversible and dose-dependent manner with the addition of a small molecule that is specific for the DD, Shield-1. Proteins encounter different local protein quality control (QC) machinery when targeted to cellular compartments such as the mitochondrial matrix or endoplasmic reticulum (ER). These varied environments could have profound effects on the levels and regulation of the cytoplasmically derived DD. Here we show that DD fusions in the cytoplasm or nucleus can be efficiently degraded in mammalian cells; however, targeting fusions to the mitochondrial matrix or ER lumen leads to accumulation even in the absence of Shield-1. Additionally, we characterize the behavior of the DD with perturbants that modulate protein production, degradation, and local protein QC machinery. Chemical induction of the unfolded protein response in the ER results in decreased levels of an ER-targeted DD indicating the sensitivity of the DD to the degradation environment. These data reinforce that DD is an effective tool for protein perturbation, show that the local QC machinery affects levels of the DD, and suggest that the DD may be a useful probe for monitoring protein quality control machinery.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.