ArticleThe Journal of biological chemistry2011
Ligand-switchable substrates for a ubiquitin-proteasome system.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Neuroprotective Potency of Neolignans inFrontiers in pharmacology · 2022Pooled it
- Episodic transport of protein aggregates achieves a positive size selectivity in aggresome formation.Nature communications · 2025Article
- Carbonic anhydrase 2-derived drug-responsive domain regulates membrane-bound cytokine expression and function in engineered T cells.Communications biology · 2025Article
- CRISPR perfect adaptation for robust control of cellular immune and apoptotic responses.Nucleic acids research · 2024Article
- Ubiquitin-Derived Fragment as a Peptide Linker for the Efficient Cleavage of a Target Protein from a Degron.ACS chemical biology · 2024Article
- A cAMP Sensor Based on Ligand-Dependent Protein Stabilization.ACS chemical biology · 2022Article
- The role of small molecules in cell and gene therapy.RSC medicinal chemistry · 2021Review
- A drug-tunable Flt23k gene therapy for controlled intervention in retinal neovascularization.Angiogenesis · 2021Article
- A Method for Conditional Regulation of Protein Stability in Native or Near-Native Form.Cell chemical biology · 2020Article
- Role for ribosome-associated quality control in sampling proteins for MHC class I-mediated antigen presentation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A technique for delineating the unfolding requirements for substrate entry into retrotranslocons during endoplasmic reticulum-associated degradation.The Journal of biological chemistry · 2019Article
- Acute unfolding of a single protein immediately stimulates recruitment of ubiquitin protein ligase E3C (UBE3C) to 26S proteasomes.The Journal of biological chemistry · 2019Article
- Misfolded GPI-anchored proteins are escorted through the secretory pathway by ER-derived factors.eLife · 2019Article
- Drug-Inducible Control of Lethality Genes: A Low Background Destabilizing Domain Architecture Applied to the Gal4-UAS System in Drosophila.ACS synthetic biology · 2018Article
- Chemogenetic Tools for Causal Cellular and Neuronal Biology.Physiological reviews · 2018Review
- An optimized, broadly applicable piggyBac transposon induction system.Nucleic acids research · 2017Article
- Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization.Nature communications · 2017Article
- Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan trimming and dislocation.Molecular biology of the cell · 2017Article
- MAP Kinase Phosphatase 3 (MKP3) Preserves Norepinephrine Transporter Activity by Modulating ERK1/2 Kinase-Mediated Gene Expression.Frontiers in cellular neuroscience · 2017Article
- A Novel Destabilizing Domain Based on a Small-Molecule Dependent Fluorophore.ACS chemical biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cellular maintenance of protein homeostasis is essential for normal cellular function. The ubiquitin-proteasome system (UPS) plays a central role in processing cellular proteins destined for degradation, but little is currently known about how misfolded cytosolic proteins are recognized by protein quality control machinery and targeted to the UPS for degradation in mammalian cells. Destabilizing domains (DDs) are small protein domains that are unstable and degraded in the absence of ligand, but whose stability is rescued by binding to a high affinity cell-permeable ligand. In the work presented here, we investigate the biophysical properties and cellular fates of a panel of FKBP12 mutants displaying a range of stabilities when expressed in mammalian cells. Our findings correlate observed cellular instability to both the propensity of the protein domain to unfold in vitro and the extent of ubiquitination of the protein in the non-permissive (ligand-free) state. We propose a model in which removal of stabilizing ligand causes the DD to unfold and be rapidly ubiquitinated by the UPS for degradation at the proteasome. The conditional nature of DD stability allows a rapid and non-perturbing switch from stable protein to unstable UPS substrate unlike other methods currently used to interrogate protein quality control, providing tunable control of degradation rates.
Indexed as
Identifiers
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.