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.