| Autor: |
Dever, T E, Chen, J J, Barber, G N, Cigan, A M, Feng, L, Donahue, T F, London, I M, Katze, M G, Hinnebusch, A G |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; May 1993, Vol. 90 Issue: 10 p4616-4620, 5p |
| Abstrakt: |
Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha) in Saccharomyces cerevisiae by the GCN2 protein kinase stimulates the translation of GCN4 mRNA. The protein kinases heme-regulated inhibitor of translation (HRI) and double-stranded RNA-dependent eIF-2 alpha protein kinase (dsRNA-PK) inhibit initiation of translation in mammalian cells by phosphorylating Ser-51 of eIF-2 alpha. We show that HRI and dsRNA-PK phosphorylate yeast eIF-2 alpha in vitro and in vivo and functionally substitute for GCN2 protein to stimulate GCN4 translation in yeast. In addition, high-level expression of either mammalian kinase in yeast decreases the growth rate, a finding analogous to the inhibition of total protein synthesis by these kinases in mammalian cells. Phosphorylation of eIF-2 alpha inhibits initiation in mammalian cells by sequestering eIF-2B, the factor required for exchange of GTP for GDP on eIF-2. Mutations in the GCN3 gene, encoding a subunit of the yeast eIF-2B complex, eliminate the effects of HRI and dsRNA-PK on global and GCN4-specific translation in yeast. These results provide further in vivo evidence that phosphorylation of eIF-2 alpha inhibits translation by impairing eIF-2B function and identify GCN3 as a regulatory subunit of eIF-2B. These results also suggest that GCN4 translational control will be a good model system to study how mammalian eIF-2 alpha kinases are modulated by environmental signals and viral regulatory factors. |
| Databáze: |
Supplemental Index |
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