Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

• Published in: PloS one 2013-06, Vol.8 (6), p.e66087-e66087
• Main Authors: Fiume, Giuseppe, Rossi, Annalisa, de Laurentiis, Annamaria, Falcone, Cristina, Pisano, Antonio, Vecchio, Eleonora, Pontoriero, Marilena, Scala, Iris, Scialdone, Annarita, Masci, Francesca Fasanella, Mimmi, Selena, Palmieri, Camillo, Scala, Giuseppe, Quinto, Ileana
• Format: Article
• Language: English
• Subjects: Biology; Blotting, Western; Cell growth; Cell proliferation; Cell survival; Chromatin Immunoprecipitation; Clinical medicine; DNA helicase; Eukaryotic Initiation Factor-4A - genetics; Eukaryotic Initiation Factor-4A - metabolism; Gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Genetic transformation; HeLa Cells; HIV; Human immunodeficiency virus; Humans; Inflammation; Inflammatory response; Initiation complex; Initiation factors; Kinases; Medicine; NF-κB protein; Phosphorylation; Protein biosynthesis; Protein synthesis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA helicase; Signaling; Transcription activation; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Transcriptional Activation - genetics; Transcriptional Activation - physiology; Transformation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066087

Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control.