YB-1 regulates stress granule formation and tumor progression by translationally activating G3BP1
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- Syam Prakash Somasekharan
- Department of Pathology and Laboratory Medicine 1 and 2
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- Amal El-Naggar
- Department of Pathology and Laboratory Medicine 1 and 2
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- Gabriel Leprivier
- Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada 3
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- Hongwei Cheng
- Department of Pathology and Laboratory Medicine 1 and 2
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- Shamil Hajee
- Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada 3
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- Thomas G.P. Grunewald
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 830, Genetics and Biology of Cancers, Institute Curie Research Center, 75248 Paris, France 4
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- Fan Zhang
- Department of Pathology and Laboratory Medicine 1 and 2
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- Tony Ng
- Department of Pathology and Laboratory Medicine 1 and 2
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- Olivier Delattre
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 830, Genetics and Biology of Cancers, Institute Curie Research Center, 75248 Paris, France 4
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- Valentina Evdokimova
- Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada 3
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- Yuzhuo Wang
- Department of Pathology and Laboratory Medicine 1 and 2
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- Martin Gleave
- Department of Pathology and Laboratory Medicine 1 and 2
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- Poul H. Sorensen
- Department of Pathology and Laboratory Medicine 1 and 2
説明
<jats:p>Under cell stress, global protein synthesis is inhibited to preserve energy. One mechanism is to sequester and silence mRNAs in ribonucleoprotein complexes known as stress granules (SGs), which contain translationally silent mRNAs, preinitiation factors, and RNA-binding proteins. Y-box binding protein 1 (YB-1) localizes to SGs, but its role in SG biology is unknown. We now report that YB-1 directly binds to and translationally activates the 5′ untranslated region (UTR) of G3BP1 mRNAs, thereby controlling the availability of the G3BP1 SG nucleator for SG assembly. YB-1 inactivation in human sarcoma cells dramatically reduces G3BP1 and SG formation in vitro. YB-1 and G3BP1 expression are highly correlated in human sarcomas, and elevated G3BP1 expression correlates with poor survival. Finally, G3BP1 down-regulation in sarcoma xenografts prevents in vivo SG formation and tumor invasion, and completely blocks lung metastasis in mouse models. Together, these findings demonstrate a critical role for YB-1 in SG formation through translational activation of G3BP1, and highlight novel functions for SGs in tumor progression.</jats:p>
収録刊行物
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- Journal of Cell Biology
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Journal of Cell Biology 208 (7), 913-929, 2015-03-23
Rockefeller University Press