ArticleOncogene2017
The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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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.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Core transcriptional regulatory circuitry identified from patient-derived tumor cells provides a specific vulnerability for rhabdomyosarcoma.Cell death & disease · 2026Article
- Combined MYC Activation and PTEN Loss Drives Molecular Features of Aggressive Preinvasive Lesions in Mouse Prostate.Molecular cancer research : MCR · 2026Article
- Anticancer drug development against ribosome synthesis and the nucleolus.Biochemical Society transactions · 2025Article
- Meioc-Piwil1 complexes regulate rRNA transcription for differentiation of spermatogonial stem cells.eLife · 2025Article
- Article
- CKLF instigates a "cold" microenvironment to promote MYCN-mediated tumor aggressiveness.Science advances · 2024Article
- Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer.Cancer discovery · 2024Article
- Hepatic depletion of nucleolar protein mDEF causes excessive mitochondrial copper accumulation associated with p53 and NRF1 activation.iScience · 2023Article
- Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.The Science of the total environment · 2023Review
- MYCN Amplification Is Associated with Reduced Expression of Genes Encoding γ-Secretase Complex and NOTCH Signaling Components in Neuroblastoma.International journal of molecular sciences · 2023Article
- Cross-linking mass spectrometry discovers, evaluates, and corroborates structures and protein-protein interactions in the human cell.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ribosome biogenesis factors-from names to functions.The EMBO journal · 2023Review
- Restoring Age-Related Cognitive Decline through Environmental Enrichment: A Transcriptomic Approach.Cells · 2022Article
- Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma.Cancer research · 2021Article
- Rcl1 depletion impairs 18S pre-rRNA processing at the A1-site and up-regulates a cohort of ribosome biogenesis genes in zebrafish.Nucleic acids research · 2021Article
- Review
- Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity.Frontiers in cell and developmental biology · 2021Review
- Ganglioneuromas are driven by activated AKT and can be therapeutically targeted with mTOR inhibitors.The Journal of experimental medicine · 2020Article
- ARID1A loss in neuroblastoma promotes the adrenergic-to-mesenchymal transition by regulating enhancer-mediated gene expression.Science advances · 2020Article
- Pediatric Cancer Models in Zebrafish.Trends in cancer · 2020Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
The nucleolar factor, digestive organ expansion factor (DEF), has a key role in ribosome biogenesis, functioning in pre-ribosomal RNA (pre-rRNA) processing as a component of the small ribosomal subunit (SSU) processome. Here we show that the peripheral sympathetic nervous system (PSNS) is very underdeveloped in def-deficient zebrafish, and that def haploinsufficiency significantly decreases disease penetrance and tumor growth rate in a MYCN-driven transgenic zebrafish model of neuroblastoma that arises in the PSNS. Consistent with these findings, DEF is highly expressed in human neuroblastoma, and its depletion in human neuroblastoma cell lines induces apoptosis. Interestingly, overexpression of MYCN in zebrafish and in human neuroblastoma cells results in the appearance of intermediate pre-rRNAs species that reflect the processing of pre-rRNAs through Pathway 2, a pathway that processes pre-rRNAs in a different temporal order than the more often used Pathway 1. Our results indicate that DEF and possibly other components of the SSU processome provide a novel site of vulnerability in neuroblastoma cells that could be exploited for targeted 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.