ArticleCell chemical biology2020
Simultaneous Control of Endogenous and User-Defined Genetic Pathways Using Unique ecDHFR Pharmacological Chaperones.
Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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.
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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
10 citing papers in PubMed, 13 citations in OpenAlex.
- Engineering Protein Stability with Small Molecules: A Review of the ecDHFR Destabilizing Domain System.ACS chemical biology · 2026Review
- Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions.Science advances · 2024Article
- Peptide-encoding gene transfer to modulate intracellular protein-protein interactions.Molecular therapy. Methods & clinical development · 2024Article
- A loss-of-function cysteine mutant in fibulin-3 (EFEMP1) forms aberrant extracellular disulfide-linked homodimers and alters extracellular matrix composition.Human mutation · 2022Article
- Development of a New DHFR-Based Destabilizing Domain with Enhanced Basal Turnover and Applicability in Mammalian Systems.ACS chemical biology · 2022Article
- Utility of the DHFR-based destabilizing domain across mouse models of retinal degeneration and aging.iScience · 2022Article
- Inclusion of a degron reduces levelsof undesired inteins after AAV-mediated proteinMolecular therapy. Methods & clinical development · 2021Article
- Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Protocol forSTAR protocols · 2020Article
- Protocol for Designing Small-Molecule-Regulated Destabilizing Domains forSTAR protocols · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Destabilizing domains (DDs), such as a mutated form of Escherichia coli dihydrofolate reductase (ecDHFR), confer instability and promote protein degradation. However, when combined with small-molecule stabilizers (e.g., the antibiotic trimethoprim), DDs allow positive regulation of fusion protein abundance. Using a combinatorial screening approach, we identified and validated 17 unique 2,4-diaminopyrimidine/triazine-based ecDHFR DD stabilizers, at least 15 of which were ineffective antibiotics against E. coli and S. aureus. Identified stabilizers functioned in vivo to control an ecDHFR DD-firefly luciferase in the mouse eye and/or the liver. Next, stabilizers were leveraged to perform synergistic dual functions in vitro (HeLa cell death sensitization) and in vivo (repression of ocular inflammation) by stabilizing a user-defined ecDHFR DD while also controlling endogenous signaling pathways. Thus, these newly identified pharmacological chaperones allow for simultaneous control of compound-specific endogenous and user-defined genetic pathways, the combination of which may provide synergistic effects in complex biological scenarios.
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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.