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Differential Requirements for eIF4E Dose in Normal Development and Cancer.
Truitt, Morgan L; Conn, Crystal S; Shi, Zhen; Pang, Xiaming; Tokuyasu, Taku; Coady, Alison M; Seo, Youngho; Barna, Maria; Ruggero, Davide.
Affiliation
  • Truitt ML; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Conn CS; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Shi Z; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Pang X; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Tokuyasu T; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Coady AM; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Seo Y; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Barna M; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: mbarna@stanford.edu.
  • Ruggero D; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Franc
Cell ; 162(1): 59-71, 2015 Jul 02.
Article in En | MEDLINE | ID: mdl-26095252
ABSTRACT
eIF4E, the major cap-binding protein, has long been considered limiting for translating the mammalian genome. However, the eIF4E dose requirement at an organismal level remains unexplored. By generating an Eif4e haploinsufficient mouse, we found that a 50% reduction in eIF4E expression, while compatible with normal development and global protein synthesis, significantly impeded cellular transformation. Genome-wide translational profiling uncovered a translational program induced by oncogenic transformation and revealed a critical role for the dose of eIF4E, specifically in translating a network of mRNAs enriched for a unique 5' UTR signature. In particular, we demonstrate that the dose of eIF4E is essential for translating mRNAs that regulate reactive oxygen species, fueling transformation and cancer cell survival in vivo. Our findings indicate eIF4E is maintained at levels in excess for normal development that are hijacked by cancer cells to drive a translational program supporting tumorigenesis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Transformation, Neoplastic / Gene Dosage / Eukaryotic Initiation Factor-4E / Embryo, Mammalian Limits: Animals Language: En Journal: Cell Year: 2015 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Transformation, Neoplastic / Gene Dosage / Eukaryotic Initiation Factor-4E / Embryo, Mammalian Limits: Animals Language: En Journal: Cell Year: 2015 Document type: Article Affiliation country: United States