ArticleACS chemical biology2019
Targeted Protein Degradation through Cytosolic Delivery of Monobody Binders Using Bacterial Toxins.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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
21 citing papers in PubMed, 39 citations in OpenAlex.
- Quantitative Degradation Rate Assessment of bioPROTACs Based on Peptide Degrons, E3 Domains, Adapters and Conjugated Small Molecules.ACS chemical biology · 2026Article
- Hydrophilic α-Aryl-α-Diazoamides for Protein Esterification.Synlett : accounts and rapid communications in synthetic organic chemistry · 2025Article
- Shiga Toxin: Emerging Producer Strains, Prophylactic Approaches, and Application in Cancer Therapy.Journal of cancer prevention · 2024Review
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- Cytosolic delivery of monobodies using the bacterial type III secretion system inhibits oncogenic BCR: ABL1 signaling.Cell communication and signaling : CCS · 2024Article
- Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons.ACS central science · 2024Article
- Improving the pharmacokinetics, biodistribution and plasma stability of monobodies.Frontiers in pharmacology · 2024Article
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Targeted intracellular delivery of Cas13 and Cas9 nucleases using bacterial toxin-based platforms.Cell reports · 2022Article
- Non-Antibody-Based Binders for the Enrichment of Proteins for Analysis by Mass Spectrometry.Biomolecules · 2021Review
- Shiga Toxins as Antitumor Tools.Toxins · 2021Review
- Selective and noncovalent targeting of RAS mutants for inhibition and degradation.Nature communications · 2021Article
- A Computational Investigation of In Vivo Cytosolic Protein Delivery for Cancer Therapy.Pharmaceutics · 2021Article
- Driving CARs with alternative navigation tools - the potential of engineered binding scaffolds.The FEBS journal · 2021Review
- Review
- Prey for the Proteasome: Targeted Protein Degradation-A Medicinal Chemist's Perspective.Angewandte Chemie (International ed. in English) · 2020Review
- Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains.Nature communications · 2020Article
- Development of light-responsive protein binding in the monobody non-immunoglobulin scaffold.Nature communications · 2020Article
- Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol.Communications biology · 2020Article
- Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms.Nature communications · 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
3 authors at 1 institution in 1 country.
Funding
Abstract
Monobodies are small engineered binding proteins that, upon expression in cells, can inhibit signaling of cytosolic oncoproteins with outstanding selectivity. Efficacy may be further increased by inducing degradation of monobody targets through fusion to the von Hippel-Lindau (VHL) substrate receptor of the Cullin2-E3 ubiquitin ligase complex. However, potential therapeutic use is currently limited, because of the inability of monobody proteins to cross cellular membranes. Here, we use a chimeric bacterial toxin, composed of the Shiga-like toxin B (Stx2B) subunit and the translocation domain of Pseudomonas aeruginosa exotoxin A (ETA-II) for delivery of VHL-monobody protein fusions to target endogenous tyrosine kinases in cancer cells. Depending on the expression of the Stx2B receptor Gb3 on the cell surface, we show that monobodies are taken up by an endocytic route, but are not degraded in lysosomes. Delivery of monobodies fused to a nuclear localization signal resulted in accumulation in the nucleus, thereby indirectly, but unequivocally, demonstrating cytosolic delivery. Delivery of VHL fused to monobodies targeting the Lck tyrosine kinase in T-cells resulted in reduced Lck protein levels, which was dependent on the expression of Gb3. This led to the inhibition of proximal signaling events downstream of the T-cell receptor complex. This work provides a prime example of the delivery of a stoichiometric protein inhibitor of an endogenous target protein to cells and inducing its degradation without the need of genetic manipulation of target cells. It lays the foundation for further in vivo exploitation of this delivery system.
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.