The role of eIF3 and its individual subunits in cancer.

ABSTRACT

Specific individual subunits of eIF3 are elevated or reduced in numerous human tumors, and their ectopic overexpression in immortal cells can result in malignant transformation. The structure and assembly of eIF3 and its role in promoting mRNA and methionyl-tRNAi binding to the ribosome during the initiation phase of protein synthesis are described. Methods employed to detect altered levels of eIF3 subunits in cancers are critically evaluated in order to conclude rigorously that such subunits may cause malignant transformation. Strong evidence is presented that the individual overexpression of eIF3 subunits 3a, 3b, 3c, 3h, 3i and 3m may cause malignant transformation, whereas underexpression of subunits 3e and 3f may cause a similar outcome. Possible mechanisms to explain the malignant phenotypes are examined. The involvement of eIF3 in cancer reinforces the view that translational control plays an important role in the regulation of cell proliferation, and provides new targets for the development of therapeutic agents. This article is part of a Special Issue entitled Translation and Cancer.