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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...
Language English Country United States
Document type Journal Article
NLK
Cell Press Free Archives
from 1997-12-01 to 1 year ago
Free Medical Journals
from 1997 to 1 year ago
Free Medical Journals
from 1997 to 1 year ago
Open Access Digital Library
from 1997-12-01
- MeSH
- Lymphoma, B-Cell enzymology genetics pathology MeSH
- B-Lymphocytes enzymology pathology MeSH
- DEAD-box RNA Helicases genetics metabolism MeSH
- Child MeSH
- Adult MeSH
- Proteostasis MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Loss of Function Mutation MeSH
- Mice, Transgenic MeSH
- Cell Line, Tumor MeSH
- Neoplasm Proteins biosynthesis genetics MeSH
- Child, Preschool MeSH
- Proteome MeSH
- Protein Biosynthesis MeSH
- Proto-Oncogene Proteins c-myc genetics metabolism MeSH
- Gene Expression Regulation, Enzymologic MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Endoplasmic Reticulum Stress MeSH
- Minor Histocompatibility Antigens genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article 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
References provided by Crossref.org
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