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Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis
C. Gong, JA. Krupka, J. Gao, NF. Grigoropoulos, G. Giotopoulos, R. Asby, M. Screen, Z. Usheva, F. Cucco, S. Barrans, D. Painter, NBM. Zaini, B. Haupl, S. Bornelöv, I. Ruiz De Los Mozos, W. Meng, P. Zhou, AE. Blain, S. Forde, J. Matthews, MG. Khim...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
NLK
Cell Press Free Archives
od 1997-12-01 do Před 1 rokem
Free Medical Journals
od 1997 do Před 1 rokem
Free Medical Journals
od 1997 do Před 1 rokem
Open Access Digital Library
od 1997-12-01
Elsevier Open Access Journals
od 1997-12-01 do 2023-06-15
Elsevier Open Archive Journals
od 1997-12-01 do Před 1 rokem
- MeSH
- B-buněčný lymfom enzymologie genetika patologie MeSH
- B-lymfocyty enzymologie patologie MeSH
- DEAD-box RNA-helikasy genetika metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- homeostáze proteinů MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace ztráty funkce MeSH
- myši transgenní MeSH
- nádorové buněčné linie MeSH
- nádorové proteiny biosyntéza genetika MeSH
- předškolní dítě MeSH
- proteom MeSH
- proteosyntéza MeSH
- protoonkogenní proteiny c-myc genetika metabolismus MeSH
- regulace genové exprese enzymů MeSH
- regulace genové exprese u nádorů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stres endoplazmatického retikula MeSH
- vedlejší histokompatibilní antigeny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also enriched in MYC-translocated diffuse large B cell lymphoma and reveal functional cooperation between mutant DDX3X and MYC. DDX3X promotes the translation of mRNA encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y chromosome homolog, the expression of which is normally restricted to the testis. These findings show that DDX3X loss of function can buffer MYC-driven proteotoxic stress and highlight the capacity of male B cell lymphomas to then compensate for this loss by ectopic DDX3Y expression.
CEITEC Masaryk University Brno Czech Republic
Department for Neuromuscular Diseases UCL Queen Square Institute of Neurology London WC1N 3BG UK
Department of Haematology Singapore General Hospital Singapore Singapore
Department of Haematology University of Cambridge Cambridge CB2 0AW UK
Department of Paediatric Oncology Addenbrooke's Hospital Cambridge UK
Frankfurt Cancer Institute Goethe University Frankfurt 60596 Frankfurt Germany
German Cancer Research Center and German Cancer Consortium Heidelberg Germany
Haematological Malignancy Diagnostic Service St James's Institute of Oncology Leeds LS9 7TF UK
Immunology Programme The Babraham Institute Cambridge CB22 3AT UK
MRC Cancer Unit University of Cambridge Hutchison MRC Research Centre Cambridge CB2 0XZ UK
National Horizons Centre Teesside University 38 John Dixon Lane Darlington DL1 1HG UK
School of Biological Sciences Nanyang Technological University 60 Nanyang Drive Singapore Singapore
School of Health and Life Sciences Teesside University Middlesbrough TS1 3BA UK
The Francis Crick Institute London NW1 1AT UK
Wellcome Trust Sanger Institute Hinxton Cambridge CB10 1SA UK
Citace poskytuje Crossref.org
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