TAILIEUCHUNG - Báo cáo khoa học: Interferon-a induces sensitization of cells to inhibition of protein synthesis by tumour necrosis factor-related apoptosis-inducing ligand

Tumour cells are often sensitized by interferons to the effects of tumour necrosis factor-a-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 Res62, 2272–2280] and we have therefore examined the consequences of prior interferon-atreatment for the sensitivity of transla-tion to inhibition by TRAIL. | ễFEBS Journal Interferon-a induces sensitization of cells to inhibition of protein synthesis by tumour necrosis factor-related apoptosis-inducing ligand Ian W. Jeffrey Androulla Elia Stephanie Bornes Vivienne J. Tilleray Karthiga Gengatharan and Michael J. Clemens TranslationalControlGroup Centre for Molecular and Metabolic Signalling Division of Basic MedicalSciences St George s University of London UK Keywords caspases interferon-a polypeptide chain initiation protein synthesis TRAIL Correspondence M. J. Clemens Division of Basic Medical Sciences St George s University of London Cranmer Terrace London SW17 0RE UK Fax 44 20 8725 2992 Tel 44 20 8725 5762 E-mail Present address Departement d Oncogenetique Centre Biomedicale de Recherche et Valorisation Clermont-Ferrand France. Received 15 March 2006 revised 19 May 2006 accepted 12 June 2006 Tumour cells are often sensitized by interferons to the effects of tumour necrosis factor-a-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-a 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 a 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-a 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 .

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