Related Experiment Video
Updated: Jun 15, 2026
08:47
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
Structural characterization of the Z RING-eIF4E complex reveals a distinct mode of control for eIF4E
Laurent Volpon1, Michael J Osborne, Althea A Capul
1Institute of Research in Immunology and Cancer, Department of Pathology and Cell Biology, Université de Montréal, Pavillion Marcelle-Coutu, Chemin Polytechnique, Montreal, QC, Canada.
Summary
Really Interesting New Gene (RING) proteins like PML and Z inhibit the oncogene eIF4E by binding to a novel site. This interaction reduces eIF4E
Area of Science:
- Molecular Biology
- Oncology
- Structural Biology
Background:
- Eukaryotic translation initiation factor 4E (eIF4E) is a key oncogene.
- eIF4E is regulated by proteins like eIF4G and 4E-binding proteins (4E-BPs) via a known binding site.
- A second class of regulators, Really Interesting New Gene (RING) proteins (e.g., PML, Z), also inhibit eIF4E function.
Purpose of the Study:
- To elucidate the structural basis of RING protein inhibition of eIF4E.
- To understand how RING proteins decrease eIF4E's affinity for its m(7)G cap ligand.
Main Methods:
- Determined the structure of the Z protein.
- Studied the Z-eIF4E complex using Nuclear Magnetic Resonance (NMR) methods.
Main Results:
- Z interacts with eIF4E through a novel binding site, distinct from eIF4G/4E-BP sites and the RING ubiquitin system site.
- Z and eIF4G bind to different regions of eIF4E, altering the m(7)G cap-binding site conformation differently.
- Provided a molecular explanation for how PML and Z RINGs inhibit eIF4E function by reducing m(7)G cap affinity.
Conclusions:
- The study reveals a novel mechanism of eIF4E regulation by RING proteins.
- Findings offer insights into the structural basis of eIF4E inhibition by PML and Z.
- The research sheds light on unique RING protein interaction modes.
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