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

Genetics
F L EricksonE M Hannig

Abstract

Eukaryotic translation initiation factor 2 (eIF2) is a G protein heterotrimer required for GTP-dependent delivery of initiator tRNA to the ribosome. eIF2B, the nucleotide exchange factor for eIF2, is a heteropentamer that, in yeast, is encoded by four essential genes and one nonessential gene. We found that increased levels of wild-type eIF2, in the presence of sufficient levels of initiator tRNA, overcome the requirement for eIF2B in vivo. Consistent with bypassing eIF2B, these conditions also suppress the lethal effect of overexpressing the mammalian tumor suppressor PKR, an eIF2alpha kinase. 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 function of eIF2B in vitro. Interestingly, the same conditions that bypass eIF2B also overcome the requirement for the normally essential eIF2alpha structural gene (SUI2). Our results suggest that the eIF2betagamma complex is capable of carrying out the essential function(s) of eIF2 in the absence of eIF2alpha and eIF2B and are consistent with the idea that the latter function primarily to regulate the level of eIF2.GTP.Met-tRNA(i)(Met) ternary complexes in vivo.

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Citations

Mar 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hui-Ren ZhouJames J Pestka
Feb 10, 2018·Biochemistry·Andrew M BogoradAssen Marintchev
Sep 13, 2005·Annual Review of Microbiology·Alan G Hinnebusch
Nov 18, 2005·Protein Expression and Purification·Rajasekhar N V S SuraganiKolluru V A Ramaiah
Dec 23, 2003·The Journal of Biological Chemistry·Antonina Roll-MecakStephen K Burley
Feb 6, 2004·The Journal of Biological Chemistry·Laure YatimeYves Mechulam
Sep 19, 2001·Yeast
Mar 11, 2004·The Journal of Investigative Dermatology·Bernd BeckerThomas Vogt
May 18, 2016·Genetics·Thomas E DeverGraham D Pavitt
May 7, 2010·The Journal of Biological Chemistry·Jon R Lorsch, Thomas E Dever
Feb 7, 2014·Annual Review of Biochemistry·Alan G Hinnebusch
Nov 10, 2009·FEBS Letters·Emmanuelle SchmittYves Mechulam

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