title: Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB.
abstract: 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.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Catanzaro, Italy. fiume@unicz.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fiume
authors.forename: Annalisa
authors.initials: A
authors.lastname: Rossi
authors.forename: Annamaria
authors.initials: A
authors.lastname: de Laurentiis
authors.forename: Cristina
authors.initials: C
authors.lastname: Falcone
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisano
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vecchio
authors.forename: Marilena
authors.initials: M
authors.lastname: Pontoriero
authors.forename: Iris
authors.initials: I
authors.lastname: Scala
authors.forename: Annarita
authors.initials: A
authors.lastname: Scialdone
authors.forename: Francesca Fasanella
authors.initials: FF
authors.lastname: Masci
authors.forename: Selena
authors.initials: S
authors.lastname: Mimmi
authors.forename: Camillo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scala
authors.forename: Ileana
authors.initials: I
authors.lastname: Quinto
mesh_terms: D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology
chemical_list: D051996:Transcription Factor RelA; D039601:Eukaryotic Initiation Factor-4A