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Translational homeostasis via the mRNA cap-binding protein, eIF4E.

Molecular cell | Jun 29, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22578813

Translational control of gene expression plays a key role in many biological processes. Consequently, the activity of the translation apparatus is under tight homeostatic control. eIF4E, the mRNA 5' cap-binding protein, facilitates cap-dependent translation and is a major target for translational control. eIF4E activity is controlled by a family of repressor proteins, termed 4E-binding proteins (4E-BPs). Here, we describe the surprising finding that despite the importance of eIF4E for translation, a drastic knockdown of eIF4E caused only minor reduction in translation. This conundrum can be explained by the finding that 4E-BP1 is degraded in eIF4E-knockdown cells. Hypophosphorylated 4E-BP1, which binds to eIF4E, is degraded, whereas hyperphosphorylated 4E-BP1 is refractory to degradation. We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination.

Pubmed ID: 22578813 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Animals | Binding Sites | Eukaryotic Initiation Factor-4E | HEK293 Cells | HeLa Cells | Homeostasis | Humans | Mice | Models, Biological | Molecular Sequence Data | Phosphoproteins | Protein Biosynthesis | RNA Cap-Binding Proteins | Transfection | Ubiquitin

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Associated grants

  • Agency: NCI NIH HHS, Id: CA51995
  • Agency: Canadian Institutes of Health Research, Id: MOP 7214
  • Agency: NCI NIH HHS, Id: P01 CA128814
  • Agency: NCI NIH HHS, Id: R01 CA051995

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