ArticleNucleic acids research2021
Effect of small molecule eRF3 degraders on premature termination codon readthrough.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Pharmacological readthrough and base editing forMolecular therapy. Nucleic acids · 2026Article
- Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research.Pharmaceutics · 2026Review
- Advances in Therapies for Mucopolysaccharidoses.Current issues in molecular biology · 2026Review
- RFFL-mediated protein quality control limits functional rescue of TRID-CFTR modulator combination therapy for cystic fibrosis nonsense mutations.Cellular and molecular life sciences : CMLS · 2026Article
- PTC124 promotes mutation site-dependent readthrough of STK11 nonsense mutations and restores tumor suppressor function.BBA advances · 2026Article
- Recovery of α-L-fucosidase in fucosidosis nonsense variants by readthrough stimulation and release factor degradation.Disease models & mechanisms · 2026Article
- Mice carrying nonsense mutant p53 develop frequent multicentric or metastatic tumors.Cell death & disease · 2025Article
- Novel eRF3a degrader enhances gentamicin-induced premature termination codon readthrough in epidermolysis bullosa.Molecular therapy. Nucleic acids · 2025Article
- Nonsense-mediated mRNA decay: a key regulatory system engaged in cancer.Cell communication and signaling : CCS · 2025Review
- Review
- Therapeutic Potential of Translational Readthrough at Disease-Associated Premature Termination Codons From Tumor Suppressor Genes.IUBMB life · 2025Review
- Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay.RNA (New York, N.Y.) · 2025Review
- Specificity of mRNA binding to proteins within the NMD machinery is influenced in cancer.Frontiers in molecular biosciences · 2025Article
- Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules.Nature genetics · 2024Article
- Developing AAV-delivered nonsense suppressor tRNAs for neurological disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Therapeutic Nonsense Suppression Modalities: From Small Molecules to Nucleic Acid-Based Approaches.Biomedicines · 2024Review
- Eukaryotic release factor 1 from Euplotes promotes frameshifting at premature stop codons in human cells.iScience · 2024Article
- Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations.Nature communications · 2024Article
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Premature termination codon (PTC) readthrough is considered a potential treatment for genetic diseases caused by nonsense mutations. High concentrations of aminoglycosides induce low levels of PTC readthrough but also elicit severe toxicity. Identifying compounds that enhance PTC readthrough by aminoglycosides or reduce their toxicity is a continuing challenge. In humans, a binary complex of eukaryotic release factors 1 (eRF1) and 3 (eRF3a or eRF3b) mediates translation termination. They also participate in the SURF (SMG1-UPF1-eRF1-eRF3) complex assembly involved in nonsense-mediated mRNA decay (NMD). We show that PTC readthrough by aminoglycoside G418 is considerably enhanced by eRF3a and eRF3b siRNAs and cereblon E3 ligase modulators CC-885 and CC-90009, which induce proteasomal degradation of eRF3a and eRF3b. eRF3 degradation also reduces eRF1 levels and upregulates UPF1 and selectively stabilizes TP53 transcripts bearing a nonsense mutation over WT, indicating NMD suppression. CC-90009 is considerably less toxic than CC-885 and it enhances PTC readthrough in combination with aminoglycosides in mucopolysaccharidosis type I-Hurler, late infantile neuronal ceroid lipofuscinosis, Duchenne muscular dystrophy and junctional epidermolysis bullosa patient-derived cells with nonsense mutations in the IDUA, TPP1, DMD and COL17A1 genes, respectively. Combination of CC-90009 with aminoglycosides such as gentamicin or ELX-02 may have potential for PTC readthrough therapy.
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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.