Journal
EMBO JOURNAL
Volume 19, Issue 24, Pages 6891-6899Publisher
OXFORD UNIV PRESS
DOI: 10.1093/emboj/19.24.6891
Keywords
double-stranded RNA; eIF-3; interferon; P56; translational regulation
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Funding
- NCI NIH HHS [CA-62220, R01 CA068782, CA-68782, P01 CA062220] Funding Source: Medline
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We report a new pathway of translation regulation that may operate in interferon-treated or virus-infected mammalian cells. This pathway is activated by P56, a protein whose synthesis is strongly induced by interferons or double-stranded RNA. Using a yeast two-hybrid screen, we identified the P48 subunit of the mammalian translation initiation factor eIF-3 as a protein that interacts with P56, The P56-P48 interaction was confirmed in human cells by co-immunoprecipitation assays and confocal microscopy, Gel filtration assays revealed that P56 binds to the large eIF-3 complex that contains P48. Purified recombinant P56 inhibited in vitro translation of reporter mRNAs in a dose-dependent fashion, and that inhibition was reversed by the addition of purified eIF-3. In vivo, expression of transfected P56 or induction of the endogenous P56 by interferon caused an inhibition of overall cellular protein synthesis and the synthesis of a transfected reporter protein. As expected, a P56 mutant that does not interact with P48 and eIF-3 failed to inhibit protein synthesis in vitro and in vivo.
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