Aberration in translation initiation and associated diseases: Role of the eukaryotic translation initiation factor 3A.

Translation control in eukaryotes contributes significantly to gene expression regulation during cellular processes, which enables rapid changes of specific proteins to maintain cellular homeostasis. Eukaryotic translation is a multiple-step process that comprised of four phases: initiation, elongation, termination and ribosome recycling. The initiation phase is rate-limiting and orchestrated by a set of eukaryotic translation initiation factors (eIFs). Defects in translation initiation can result in a series of diseases. Among all eIFs, eIF3 is the largest and less-known initiation factor due to its intrinsic complexity. Aberration in eIF3A, the largest subunit of eIF3, is known to contribute to carcinogenesis and protection against evolution into higher-grade malignancy, and the altered expression or mutation of eIF3A affects the responses of cancer patients to platinum-based chemotherapy. Besides its role in cancinogenesis, eIF3A is also implicated in fibrosis, and the agents inhibiting eIF3A delay the progression of this disorder. The dual roles of eIF3A in tumorigenesis are probably due to the regulation of translation of different mRNAs at different stages of tumor progression by eIF3A. In turn the encoded products serve as pro-tumor or anti-tumor proteins at different stages.