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Interferon‐α induces sensitization of cells to inhibition of protein synthesis by tumour necrosis factor‐related apoptosis‐inducing ligand
Author(s) -
Jeffrey Ian W.,
Elia Androulla,
Bornes Stéphanie,
Tilleray Vivienne J.,
Gengatharan Karthiga,
Clemens Michael J.
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05374.x
Subject(s) - sensitization , interferon , apoptosis , dephosphorylation , protein biosynthesis , downregulation and upregulation , initiation factor , tumor necrosis factor alpha , protein kinase r , translation (biology) , hela , cancer research , biology , ligand (biochemistry) , microbiology and biotechnology , phosphorylation , immunology , phosphatase , cell , protein kinase a , receptor , biochemistry , messenger rna , cyclin dependent kinase 2 , gene
Tumour cells are often sensitized by interferons to the effects of tumour necrosis factor‐α‐related apoptosis‐inducing ligand (TRAIL). We have demonstrated previously that TRAIL has an inhibitory effect on protein synthesis [Jeffrey IW, Bushell M, Tilleray VJ, Morley S & Clemens MJ (2002) Cancer Res 62 , 2272–2280] and we have therefore examined the consequences of prior interferon‐α treatment for the sensitivity of translation to inhibition by TRAIL. Interferon treatment alone has only a minor effect on protein synthesis but it sensitizes both MCF‐7 cells and HeLa cells to the downregulation of translation by TRAIL. The inhibition of translation is characterized by increased phosphorylation of the α subunit of eukaryotic initiation factor eIF2 and dephosphorylation of the eIF4E‐binding protein 4E‐BP1. Both of these effects, as well as the decrease in overall protein synthesis, require caspase‐8 activity, although they precede overt apoptosis by several hours. Interferon‐α enhances the level and/or the extent of activation of caspase‐8 by TRAIL, thus providing a likely explanation for the sensitization of cells to the inhibition of translation.