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Mitotic phosphorylation of eukaryotic initiation factor 4G1 (eIF4G1) at Ser1232 by Cdk1:cyclin B inhibits eIF4A

Mikhail I Dobrikov1, Mayya Shveygert, Michael C Brown

  • 1Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.

Molecular and Cellular Biology
|November 20, 2013
PubMed

Insights

During mitosis, cyclin-dependent kinase 1 (Cdk1) phosphorylates eukaryotic initiation factor 4G1 (eIF4G1) at Ser1232. This phosphorylation inhibits translation initiation factor activity, contributing to the global translation suppression observed during cell division.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Global protein synthesis is suppressed during mitosis, yet synthesis of essential mitotic proteins continues.
  • Evidence suggests this mitotic translation shift is regulated at the initiation step.
  • Specific molecular signals targeting translation initiation factors during mitosis remained unidentified.

Purpose of the Study:

  • To investigate the role of eukaryotic initiation factor 4G1 (eIF4G1), a key scaffold in translation initiation.
  • To identify specific phosphorylation events on eIF4G1 during mitosis.
  • To elucidate the mechanism linking eIF4G1 phosphorylation to the mitotic translation shift.

Main Methods:

  • Phosphoproteomics analysis of interphase and mitotic cells.
  • Kinase inhibition assays and in vitro phosphorylation experiments.
  • Kinase depletion-reconstitution studies.

Main Results:

  • Identified Serine 1232 (Ser1232) on eIF4G1 as a phosphorylation site during mitosis.
  • Demonstrated that cyclin-dependent kinase 1 (Cdk1):cyclin B phosphorylates eIF4G1 at Ser1232.
  • Showed that Ser1232 phosphorylation enhances eIF4A interaction with eIF4G and reduces RNA binding of the eIF4G/-4A complex.
  • Phosphorylation of eIF4G1(Ser1232) by Cdk1:cyclin B inhibits eIF4A helicase activity.

Conclusions:

  • Phosphorylation of eIF4G1 at Ser1232 by Cdk1:cyclin B is a key event in the mitotic translation initiation shift.
  • This phosphorylation event contributes to the regulation of global translation during mitosis.
  • The findings provide a molecular mechanism for controlling protein synthesis during cell division.

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