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Review
. 2013 Oct;70(19):3603-16.
doi: 10.1007/s00018-013-1263-y. Epub 2013 Jan 25.

The translational factor eIF3f: the ambivalent eIF3 subunit

Roberta Marchione  1 , Serge A Leibovitch, Jean-Luc Lenormand
Affiliations
Review

The translational factor eIF3f: the ambivalent eIF3 subunit

Roberta Marchione et al. Cell Mol Life Sci. 2013 Oct.

Abstract

The regulation of the protein synthesis has a crucial role in governing the eukaryotic cell growth. Subtle changes of proteins involved in the translation process may alter the rate of the protein synthesis and modify the cell fate by shifting the balance from normal status into a tumoral or apoptotic one. The largest eukaryotic initiation factor involved in translation regulation is eIF3. Amongst the 13 factors constituting eIF3, the f subunit finely regulates this balance in a cell-type-specific manner. Loss of this factor causes malignancy in several cells, and atrophy in normal muscle cells. The intracellular interacting partners which influence its physiological significance in both cancer and muscle cells are detailed in this review. By delineating the global interaction network of this factor and by clarifying its intracellular role, it becomes apparent that the f subunit represents a promising candidate molecule to use for biotherapeutic applications.

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Figures

Fig. 1
Fig. 1
Schematic representation of the intracellular interacting partners of the eIF3f subunit
Fig. 2
Fig. 2
Schematic representation of eIF3f interactions during apoptosis. Upon apoptotic stimulation, CDK11p110 is cleaved by caspase 3 to generate a CDKp46 that interacts strongly with the Mov34 domain of eIF3f and phosphorylates it at Ser46 and Thr119. According to Wen et al.’s [56] hypothesis (left side), phosphorylated eIF3f interacts with hnRNP K and promotes rRNA degradation by interfering with rRNA protective function of hnRNP. According to Walter et al.’s [73] hypothesis, under normal conditions (right side), Mss4 is tightly bound to eIF3f, inhibiting its phosphorylation and subsequent association with eIF3 protein complex and pro-apoptotic functions. After prolonged stress-induced apoptosis, Mss4 is downregulated, leading to a release of eIF3f, which is phosphorylated by the CDK11p46 kinase and the translation initiation results inhibited
Fig. 3
Fig. 3
Schematic representation of the intracellular signals characterizing the hypertrophic (upper panel) and atrophic (lower panel) pathways in muscle cells. During hypertrophy, mTOR phosphorylates S6K1, which is released from eIF3 complex, and phosphorylated again by PDK1. Activated S6K1 phosphorylates eIF4B, which promotes the recruitment of other initiation factors and the translation of mRNAs encoding proteins involved in muscle growth. During atrophy, the ubiquitin ligase MAFbx is upregulated and S6K1 is accumulated in its inactive hypophosphorylated form. By binding the Mov34 domain, MAFbx transfers polyubiquitin chains on eIF3f and promotes its degradation by the proteasome and block the synthesis of proteins involved in muscle cell growth
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