eIF3e: Proteins and Enzymes

Int6 is a candidate tumor suppressor in multiple neoplasms, and in particular, breast and lung cancers. The Int6 locus was initially identified as a common insertion site (CIS) in a genetic screen for transforming sequences in a breast cancer mouse model system. Insertion of mouse mammary tumor virus (MMTV) into this locus results in the production of an amino-terminal truncated gene product. Expression of the truncated Int6 product corresponds to cellular transformation in both in vivo and in vitro systems. This gene product plays a role in regulating translation initiation and is a component of the eIF3 translation initiation complex. There is evidence that suggests that Int6 may impart a negative role in the general translational machinery while promoting an increase in the expression of a subset of stressresponsive genes. Taken together, it is of great interest to further study the mechanism by which Int6 is involved in regulating cell growth.