Eukaryotic gene expression is a process mainly regulated at the levels of gene transcription and mRNA translation. Deregulation of translation (initiation, elongation, termination, recycling) results in abnormal gene expression, and thus leads to uncontrolled cell growth potentially resulting in cancer formation. The major players in canonical translation initiation are the eukaryotic translation initiation factors (eIFs), comprising eIF1, eIF1a, eIF2, eIF2b, eIF3, eIF4a, eIF4e, eIF4g, eIF4b, eIF4h, eIF5 and eIF5b. The canonical process is primed by formation of the 43S preinitiation complex, to which mRNA is recruited together with the eIF4F complex and the poly(A) binding protein (PABP). The 43S pre-initiation complex consists of the small 40S ribosomal subunit, the initiating methionyl-tRNA bound to eIF2-GTP (eIF2-GTP-MettRNAi is also known as the ternary complex) and eIFs 1, 1a and 3. Subsequently, the mRNA is scanned for the first AUG in the 50UTR until correct binding of tRNA anticodon loop to the initiator AUG on the mRNA assisted by eIF1. 
The scanning process is facilitated by eIF1 and eIF1a by altering the structure of the mRNA-binding cleft. This interaction enables functional 80S ribosome assembly on the mRNA and translation to take place. eIF3 is believed to function as a scaffold, interacting with other eIFs and the 40S ribosome. The eIF4F complex fulfils a number of tasks in translation initiation, including the scanning process. eIF4e binds to mRNA’s cap structure, eIF4a possesses helicase activity and is suggested to be positioned by eIF4g at the ribosomal mRNA entry channel. An altered translation initiation and therefore changed gene expression is increasing the risk of cancer development. Indeed, previous work showed that dysregulation of many eIFs is associated with malignant transformation and cancer progression.

References

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