{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Volegova MP"],"funding":["NCATS NIH HHS","Alex's Lemonade Stand Foundation for Childhood Cancer","NCI NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["114134"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11284644"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(5)"],"pubmed_abstract":["Tumor MYCN amplification is seen in high-risk neuroblastoma, yet direct targeting of this oncogenic transcription factor has been challenging. Here, we take advantage of the dependence of MYCN-amplified neuroblastoma cells on increased protein synthesis to inhibit the activity of eukaryotic translation initiation factor 4A1 (eIF4A1) using an amidino-rocaglate, CMLD012824. Consistent with the role of this RNA helicase in resolving structural barriers in 5' untranslated regions (UTRs), CMLD012824 increased eIF4A1 affinity for polypurine-rich 5' UTRs, including that of the MYCN and associated transcripts with critical roles in cell proliferation. CMLD012824-mediated clamping of eIF4A1 spanned the full lengths of mRNAs, while translational inhibition was mediated through 5' UTR binding in a ca"],"journal":["Cell reports"],"pubmed_title":["The MYCN 5' UTR as a therapeutic target in neuroblastoma."],"pmcid":["PMC11284644"],"funding_grant_id":["R35 GM118173","R21 CA267521","U01 TR002625"],"pubmed_authors":["Banerjee U","George RE","Sharma B","Kennedy A","Volegova MP","Porco JA","Dries R","Brown LE"],"additional_accession":[]},"is_claimable":false,"name":"The MYCN 5' UTR as a therapeutic target in neuroblastoma.","description":"Tumor MYCN amplification is seen in high-risk neuroblastoma, yet direct targeting of this oncogenic transcription factor has been challenging. Here, we take advantage of the dependence of MYCN-amplified neuroblastoma cells on increased protein synthesis to inhibit the activity of eukaryotic translation initiation factor 4A1 (eIF4A1) using an amidino-rocaglate, CMLD012824. Consistent with the role of this RNA helicase in resolving structural barriers in 5' untranslated regions (UTRs), CMLD012824 increased eIF4A1 affinity for polypurine-rich 5' UTRs, including that of the MYCN and associated transcripts with critical roles in cell proliferation. CMLD012824-mediated clamping of eIF4A1 spanned the full lengths of mRNAs, while translational inhibition was mediated through 5' UTR binding in a ca","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-02T23:35:09.754Z","creation":"2025-04-19T13:12:24.609Z"},"accession":"S-EPMC11284644","cross_references":{"pubmed":["38662542"],"doi":["10.1016/j.celrep.2024.114134"]}}