The interaction between interferon-induced protein with tetratricopeptide repeats-1 and eukaryotic elongation factor-1A

Abstract

It has been shown previously that in mammalian cells, interferon-induced protein with tetratricopeptide repeats-1(IFIT1) is rapidly synthesized in response to viral infection, functions as an inhibitor of translation by binding to the eukaryotic initiation factor-3, and consequently assigns resistive activity against viral invasion to cells. It has also been reported that IFIT1 is rapidly produced in response to other cell stress agents with no direct relation to virus such as bacterial lipopolysaccharide and interleukin-1, but its function under these non-viral infection cell stress conditions has yet to be elucidated. Here, we demonstrate an interaction between IFIT1 and eukaryotic elongation factor-1A (eEF1A) both in vitro, using recombinant proteins as bait in pull-down assays, and in vivo, using laser confocal microscopy and immunoprecipitation. In addition, we report the initial determination of the domain of IFIT1 that mediates this interaction. We also display that both IFIT1 and eEF1A protein levels are rapidly elevated, prolonged in tumor necrosis factor alpha pre-treated Raw264.7 cells, and most of those cells are induced to death by the end of investigations. Our results imply that under some stressful stimulations IFIT1 may participate in cell death pathways by interaction with eEF1A.

Unphosphorylated STAT1 represses apoptosis in macrophages during Mycobacterium t uberculosis infection

“…IFIT1 acts as an infection resistor by suppressing protein translation (Guo et al, 2000;Hui et al, 2005), and lipopolysaccharide or TNF stimulation rapidly activates IFIT1 transcription (Smith and Herschman, 1996;Wathelet et al, 1987). A previous study has shown that coupling with IFIT1 results in a change of eEF1A activity and subsequent stress-induced cell apoptosis, suggesting that this complex may accumulate during the early stages of infection and be involved in the processes of cell apoptosis (Li et al, 2010). We observed the levels of IFIT1 and eEF1A in RAW264.7 cells infected by H37Ra.…”

“…A recent study has pointed out that the interaction of interferon-induced protein tetratricopeptide repeats-1 (IFIT1) and eEF1A complex is involved in the processes of apoptosis induced by TNF in macrophages (Li et al, 2010). In order to assess whether or not IFIT1 and eEF1A protein levels in RAW264.7 cells are affected by H37Ra infection, immunoblotting analysis was performed and the levels of the proteins determined by densitometric analysis of band intensities standardized with internal control.…”

Systems-based approach to examine the cytokine responses in primary mouse lung macrophages infected with low pathogenic avian Influenza virus circulating in South East Asia

“…It is an antiviral protein for viruses that bear 5′-triphosphate RNA [45], however recently it was reported to have no effect on negative sense RNA viruses including influenza [46]. Raw264.7 cells pre-treated with TNFα presented with an elevated level of IFIT1 induced cell death [47]. In line with this, in H1N1/WSN and H5N3 virus infection an elevated level of IFIT1 was associated with increased expression of anti-apoptotic genes XIAP associated factor 1 ( XAF1 ) in both viruses and TNF receptor-associated factor 1 ( TRAF1 ) in H5N3 virus infection  (Fig.…”

A Novel Intracellular Isoform of Matrix Metalloproteinase-2 Induced by Oxidative Stress Activates Innate Immunity

“…The interferon-induced proteins with tetratricopeptide repeats 1–3 (IFIT1–3) interfere with ribosomal assembly and block interaction with eIF3 subunits, thereby inhibiting translation of viral and cellular proteins [49]. IFIT proteins also inhibit protein translation via interaction with eukaryotic elongation factor-1A [49].…”