Open AccessTranslational control of the activation of transcription factor NF-κB and production of type I interferon by phosphorylation of the translation factor eIF4E
Author(s) -
Barbara Herdy,
Maritza Jaramillo,
Yuri V. Svitkin,
Amy Rosenfeld,
Mariko Kobayashi,
Derek Walsh,
Tommy Alain,
Polen Sean,
Nathaniel Robichaud,
Ivan Topisirović,
Luc Furic,
Ryan J.O. Dowling,
Annie Sylvestre,
Rong Liang,
Rodney Colina,
Mauro Costa-Mattioli,
Jörg H. Fritz,
Martin Olivier,
Earl G. Brown,
Ian Mohr,
Nahum Sonenberg
Publication year - 2012
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/ni.2291
Subject(s) - eif4e , phosphorylation , initiation factor , interferon , biology , transcription factor , translation (biology) , eukaryotic translation , messenger rna , protein biosynthesis , microbiology and biotechnology , interferon regulatory factors , eukaryotic initiation factor , virology , genetics , gene
Type I interferon is an integral component of the antiviral response, and its production is tightly controlled at the levels of transcription and translation. The eukaryotic translation-initiation factor eIF4E is a rate-limiting factor whose activity is regulated by phosphorylation of Ser209. Here we found that mice and fibroblasts in which eIF4E cannot be phosphorylated were less susceptible to virus infection. More production of type I interferon, resulting from less translation of Nfkbia mRNA (which encodes the inhibitor IκBα), largely explained this phenotype. The lower abundance of IκBα resulted in enhanced activity of the transcription factor NF-κB, which promoted the production of interferon-β (IFN-β). Thus, regulated phosphorylation of eIF4E has a key role in antiviral host defense by selectively controlling the translation of an mRNA that encodes a critical suppressor of the innate antiviral response.