The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma
| العنوان: | The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma |
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| المؤلفون: | Susan J. Baserga, Hui Shi, Jinrong Peng, Ting Tao, A T Look, Samuel B. Sondalle, Shizhen Zhu, Antonio R. Perez-Atayde |
| المصدر: | Oncogene |
| بيانات النشر: | Nature Publishing Group, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Ribosome biogenesis, Gene Expression, Apoptosis, Haploinsufficiency, N-Myc Proto-Oncogene Protein, 03 medical and health sciences, Neuroblastoma, Growth factor receptor, Cell Line, Tumor, Genetics, medicine, RNA, Ribosomal, 18S, Animals, Humans, RNA Processing, Post-Transcriptional, RRNA processing, Molecular Biology, Zebrafish, neoplasms, Cell Proliferation, biology, fungi, Nuclear Proteins, Cell cycle, Zebrafish Proteins, biology.organism_classification, medicine.disease, Molecular biology, Cell biology, Tumor Burden, 030104 developmental biology, Original Article |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1476-5594 0950-9232 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1026bde2c08def08ed1329a698eff9f http://europepmc.org/articles/PMC5501763 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a1026bde2c08def08ed1329a698eff9f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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