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1 záznamů v Medvik

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Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis

Gong, Chun
Autor Gong, Chun Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK
Krupka, Joanna A
Autor Krupka, Joanna A Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge CB2 0XZ, UK
Gao, Jie
Autor Gao, Jie Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK
Grigoropoulos, Nicholas F
Autor Grigoropoulos, Nicholas F Department of Haematology, Singapore General Hospital, Singapore, Singapore
Giotopoulos, George
Autor Giotopoulos, George Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK
Asby, Ryan
Autor Asby, Ryan Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK
Screen, Michael
Autor Screen, Michael Immunology Programme, The Babraham Institute, Cambridge CB22 3AT, UK
Usheva, Zelvera
Autor Usheva, Zelvera Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK
Cucco, Francesco
Autor Cucco, Francesco Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB20QQ, UK
Barrans, Sharon
Autor Barrans, Sharon Haematological Malignancy Diagnostic Service, St. James's Institute of Oncology, Leeds LS9 7TF, UK

Molecular cell. 2021 ; 81 (19) : 4059-4075.e11. [pub] 20210825

Mol Cell
ISSN 1097-4164
Medvik
Zdroj

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.

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Cucco, Francesco* Dotaz Zobrazit nápovědu

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