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Review
. 2018 Feb:48:82-88.
doi: 10.1016/j.gde.2017.11.001. Epub 2017 Nov 16.

Translation initiation factors and their relevance in cancer

Columba de la Parra  1 , Beth A Walters  1 , Phillip Geter  1 , Robert J Schneider  2
Affiliations
Review

Translation initiation factors and their relevance in cancer

Columba de la Parra et al. Curr Opin Genet Dev. 2018 Feb.

Abstract

Deregulation of several translation initiation factors occurs in numerous types of cancers. Translation initiation factors are not merely ancillary players in cancer development and progression, but rather, they are key participants in cellular transformation and tumor development. In fact, the altered expression of translation initiation factors is involved in cancer cell survival, metastasis and tumor angiogenesis. Although the exact mechanisms remain to be fully characterized, translation initiation factors comprise novel targets for pharmacologic intervention. Here we review the most recently established roles of initiation factors in cancer development and progression, as well as unique methods used to study translational regulation.

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Conflict of interest statement

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1|
Figure 1|. Overview of key steps in mRNA translation initiation.
The 40S ribosomal subunit interacts with eIF1,eIF1A, eIF3, eIF5 and the ternary complex (eIF2/GTP/Met-tRNAi) forming the 43S pre-initiation complex. The assembly of the eIF4F complex (eIF4G, eIF4E and eIF4A) on the m7GpppN “cap” facilitates the recruitment of the 43S PIC to the mRNA via eIF4G-eIF3 interaction. The interaction of PABP with the scaffolding protein eIF4G might promote the circularization of the mRNA, at least for some part of initiation. eIF4A, a helicase, unwinds the mRNA, with single strand RNA binding protein eIF4B. The eIF4E-mRNA cap complex with eIF4G-eIF3, comprise the 48S ribosomal complex, which progressively searches for the translation initiation codon (typically an AUG). AUG recognition is promoted by hydrolysis of GTP bound to eIF2, an essential step for stable 60S ribosomal subunit recruitment and formation of an active 80S ribosome to initiate protein synthesis. eIF5A promotes peptide bond formation and translation elongation. The inactive eIF2-GDP is recycled to active eIF2-GTP by GTP recycling factor eIF2B.
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