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Mol Cell. 2012 Jun 29;46(6):847-58. doi: 10.1016/j.molcel.2012.04.004. Epub 2012 May 10.

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

Author information

1
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3A 1A3, Canada.

Abstract

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.

PMID:
22578813
PMCID:
PMC4085128
DOI:
10.1016/j.molcel.2012.04.004
[Indexed for MEDLINE]
Free PMC Article

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