ArticleOpen biology2017
Targeting endogenous proteins for degradation through the affinity-directed protein missile system.
Article in Open biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The trial behind it
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Who cites it
50 citing papers in PubMed, 87 citations in OpenAlex.
- Ratiometric transcriptional activation by protein degradation.bioRxiv : the preprint server for biology · 2026Article
- A nanobody-based proteolysis-targeting chimera offers broad-spectrum protection against diverse influenza virus infections.Signal transduction and targeted therapy · 2026Article
- Specific proteolysis mediated by a p97-directed proteolysis-targeting chimera (p97-PROTAC).eLife · 2025Article
- Inducible tag-free degradation of endogenous proteins with AlissAID and development of a photoactivable inducer.Communications biology · 2025Article
- Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Synthetic protein degradation circuits using programmable cleavage and ligation by Sortase A.Nature communications · 2025Article
- Artificial targeting of autophagy components to mitochondria reveals both conventional and unconventional mitophagy pathways.Autophagy · 2025Article
- Cytosolic delivery of monobodies using the bacterial type III secretion system inhibits oncogenic BCR: ABL1 signaling.Cell communication and signaling : CCS · 2024Article
- Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes.Communications biology · 2024Article
- Rapid depletion of target proteins in plants by an inducible protein degradation system.The Plant cell · 2024Article
- Lipid-mediated intracellular delivery of recombinant bioPROTACs for the rapid degradation of undruggable proteins.Nature communications · 2024Article
- Off-target autophagy inhibition by SHP2 allosteric inhibitors contributes to their antitumor activity in RAS-driven cancers.The Journal of clinical investigation · 2024Article
- Article
- Intracellular Degradation of SARS-CoV-2 N-Protein Caused by Modular Nanotransporters Containing Anti-N-Protein Monobody and a Sequence That Recruits the Keap1 E3 Ligase.Pharmaceutics · 2023Article
- Modular Nanotransporters Capable of Causing Intracellular Degradation of the N-Protein of the SARS-CoV-2 Virus in A549 Cells with Temporary Expression of This Protein Fused with a Fluorescent Protein mRuby3.Doklady. Biochemistry and biophysics · 2023Article
- Quantitative Description of the N-Protein of the SARS-CoV-2 Virus Degradation in Cells Stably Expressing It under the Influence of New Modular Nanotransporters.Doklady. Biochemistry and biophysics · 2023Article
- Development of AlissAID system targeting GFP or mCherry fusion protein.PLoS genetics · 2023Article
- A ubiquitination-mediated degradation system to target 14-3-3-binding phosphoproteins.Heliyon · 2023Article
- Monobody Inhibitor Selective to the Phosphatase Domain of SHP2 and its Use as a Probe for Quantifying SHP2 Allosteric Regulation.Journal of molecular biology · 2023Article
- Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins.
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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.