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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
The oncogene eIF4E reprograms the nuclear pore complex to promote mRNA export and oncogenic transformation
Biljana Culjkovic-Kraljacic1, Aurélie Baguet, Laurent Volpon
1Institute for Research in Immunology and Cancer, Department of Pathology and Cell Biology, Université de Montréal, Québec, Canada.
Cell Reports
|August 21, 2012
Summary
The oncogene eIF4E reprograms the nuclear pore complex (NPC) to enhance mRNA export. This mechanism involves reducing RanBP2, which normally inhibits export, thus promoting cancer cell growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The eukaryotic translation initiation factor eIF4E is a known oncogene.
- eIF4E promotes nuclear export and translation of specific mRNA transcripts.
- The nuclear pore complex (NPC) regulates transport between the nucleus and cytoplasm.
Purpose of the Study:
- To investigate how eIF4E influences mRNA export.
- To elucidate the role of the NPC in eIF4E-mediated oncogenesis.
Main Methods:
- Investigated the interaction between eIF4E and the NPC.
- Utilized genetic and pharmacological inhibition of eIF4E.
- Examined the effects of RanBP2 overexpression on eIF4E's pathway.
Main Results:
- eIF4E alters the NPC's cytoplasmic face, enhancing mRNA export.
- eIF4E reduces RanBP2 levels, a key component of NPC cytoplasmic fibrils.
- eIF4E also affects Nup214, RanBP1, Gle1, and DDX19 localization.
- RanBP2 overexpression inhibits eIF4E's mRNA export pathway and oncogenic transformation.
Conclusions:
- Oncogenes like eIF4E can reprogram the NPC to promote cell proliferation.
- Altering NPC function is a strategy employed by oncogenes to enhance cellular capacity.
- RanBP2's inhibitory role in export factor recycling is overcome by eIF4E.
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