Minimum requirements, for the function of eukaryotic translation initiation factor 2

Eukaryotic translation initiation factor 2 (eIF2) is a G protein heterotrim er required for GTP-dependent delivery of initiator tRNA to the ribosome. e IF2B, the nucleotide exchange factor for eIF2, is a heteropentamer that, in yeast, is encoded by four essential genes and one nonessential gene. We fo und that increased levels of wild-type eIF2, in the presence of sufficient levels of initiator tRNA, overcome the requirement for eIF2B in vivo. Consi stent with bypassing eIF2B, these conditions also suppress the lethal effec t of overexpressing the mammalian tumor suppressor PKR, an eIF2 alpha kinas e. The effects described are further enhanced in the presence of a mutation in the G protein (gamma) subunit of eIF2, gcd11-K250R which mimics the fun ction of eIF2B in vitro. Interestingly, the same conditions that bypass eIF 2B also overcome the requirement for the normally essential eIF2 alpha stru ctural gene (SUI2). Our results suggest that the eIF2 beta gamma complex is capable of carrying out tile essential function(s) of eIF2 in the absence of eIF2a: and eIF2B and are consistent with the idea that the latter functi on primarily to regulate the level of eIF2.GTP.Met-tRNA(i)(Met) ternary com plexes in vivo.