Recycling and phosphorylation of eukaryotic initiation factor 2 on 60S subunits of 80S initiation complexes and polysomes.
- 15 December 1992
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 89 (24) , 12063-12067
- https://doi.org/10.1073/pnas.89.24.12063
Abstract
Phosphorylation of the alpha-subunit (38 kDa) of eukaryotic initiation factor 2 (eIF-2 alpha) regulates initiation of protein synthesis in eukaryotic cells. This phosphorylation is enhanced in cycloheximide-treated heme-deficient reticulocyte lysates in which polysomes are maintained. In early heme deficiency prior to polysome disaggregation, eIF-2(alpha P) accumulates primarily on the 60S subunits of polysomes. Further, isolated polysomes contain eIF-2 alpha that is efficiently phosphorylated in vitro by heme-regulated inhibitor (HRI). Immunoblot analysis of eIF-2 distribution in sucrose gradients of actively protein-synthesizing lysates indicates that eIF-2 is distributed at low levels throughout the polysome profiles. These findings suggest that polysome-bound eIF-2 alpha is a target of HRI under physiological conditions. The presence of eIF-2 on the 60S subunits of polysomes is incompatible with the conventional model in which eIF-2 is recycled during the joining of the 48S preinitiation complex and the 60S subunit to form the 80S initiation complex. A modified model is presented with emphasis on the translocation of eIF-2 from the 40S ribosomal subunit of the 48S preinitiation complex (eIF-2.GTP.Met-tRNA(f).40S.mRNA) to the 60S subunit of the 80S initiation complex.Keywords
This publication has 31 references indexed in Scilit:
- REGULATION OF POLYPEPTIDE-CHAIN INITIATION IN CHINESE-HAMSTER OVARY CELLS WITH A TEMPERATURE-SENSITIVE LEUCYL-TRANSFER RNA-SYNTHETASE - CHANGES IN PHOSPHORYLATION OF INITIATION-FACTOR EIF-2 AND IN THE ACTIVITY OF THE GUANINE-NUCLEOTIDE EXCHANGE FACTOR GEF1987
- The association of NADPH with the guanine nucleotide exchange factor from rabbit reticulocytes: a role of pyridine dinucleotides in eukaryotic polypeptide chain initiation.Proceedings of the National Academy of Sciences, 1986
- The 60 S ribosomal subunit as a carrier of eukaryotic initiation factor 2 and the site of reversing factor activity during protein synthesis.Journal of Biological Chemistry, 1985
- Poliovirus replicase stimulation by terminal uridylyl transferase.Journal of Biological Chemistry, 1985
- Regulation of a protein synthesis initiation factor by adenovirus virus-associated RNAINature, 1985
- Distribution of reversing factor in reticulocyte lysates during active protein synthesis and on inhibition by heme deprivation or double-stranded RNA.Proceedings of the National Academy of Sciences, 1984
- A GDP/GTP exchange factor essential for eukaryotic initiation factor 2 cycling in Ehrlich ascites tumor cells and its regulation by eukaryotic initiation factor 2 phosphorylation.Journal of Biological Chemistry, 1983
- Assembly and breakdown of mammalian protein synthesis initiation complexes: regulation by guanine nucleotides and by phosphorylation of initiation factor eIF-2Biochemistry, 1983
- Protein synthesis in rabbit reticulocytes: characteristics of the protein factor RF that reverses inhibition of protein synthesis in heme-deficient reticulocyte lysates.Proceedings of the National Academy of Sciences, 1982
- Mechanism of polypeptide chain initiation in eukaryotes and its control by phosphorylation of the alpha subunit of initiation factor 2.Proceedings of the National Academy of Sciences, 1982