Translation Initiation Featured Collection

It is well established that the regulation of protein expression via mRNA translation is intimately coupled to cell growth and cell cycle progression. In light of this, translational pathophysiology is increasingly becoming recognized as a mechanism for human disease, especially cancer. The translation of mRNA into protein is a complex multi-staged process that includes the phases of initiation, elongation, and termination. The translational machinery includes an array of proteins, and although many of these proteins have been implicated in the genesis of human disease, it has been difficult to establish causal relationships. Disease may arise via subtle changes in the translation initiation apparatus or changes in regulatory mechanisms such as signaling via phosphorylation of translation factors, the regulation of micro-RNAS, or mRNA degradation. Studies have shown that over expression or over-activation of translation factors can lead to cell proliferation and transformation. Furthermore, increased levels of initiation factors have been shown to be present in tumors, and there is evidence that a combined analysis of eIF4E and 4E-BP expression is a strong prognostic indicator of breast cancer. Additionally, over-expression of specific eIF3 subunits can be detected in a variety of cancers such as breast, cervical, esophageal, lung, testicular, prostate, gastric, and hepatocellular cancers. Further understanding of the complex and multi-faceted regulation of translation and its relationship to disease is important and will allow the development of therapeutic treatments and interventions for translation-related disorders such as cancer.

Referenced Review:
Hershey, J.W.B. Regulation of protein synthesis and the role of eIF3 in cancer. 2010. Braz. J. Med. Biol. Res. 43(10) 920-930.