Translational control by adenovirus: lack of virus-associated RNAI during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis.
- 1 April 1985
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 82 (7), 1959-1963
- https://doi.org/10.1073/pnas.82.7.1959
Abstract
The d1331 mutant of adenovirus serotype 5 fails to produce virus-associated (VA) RNAI, and cells infected with this mutant do not synthesize proteins efficiently at late times in infection. The translational defect occurs at the level of polypeptide chain initiation, and cell-free extracts prepared from d1331-infected cells exhibit the defect observed in vivo. Addition of either eukaryotic initiation factor 2 (eIF-2) or guanine nucleotide exchange factor (GEF) to these cell-free extracts restores translational activity, with GEF functioning more efficiently in this regard. These results suggest that cells infected with the d1331 mutant develop a translational block at the level of GEF-catalyzed guanine nucleotide exchange and that this block is most likely established through phosphorylation of the .alpha. subunit of eIF-2. In the present investigation it is shown that endogenous HeLa cell GEF activity is significantly reduced in cells infected with the d1331 mutant. In contrast to cells infected with wild-type serotype 2 adenovirus, d1331-infected cells contain increased eIF-2.alpha. kinase activity. These results indicate that VA RNA1 plays a role in suppressing eIF-2.alpha. kinase activity during adenovirus infection of HeLa cells.Keywords
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