title: Continuous heat shock enhances translational initiation directed by internal ribosomal entry site.
abstract: Many cellular mRNAs contain internal ribosomal entry sites (IRES) that become functional under conditions of cellular stress, when the rate of protein synthesis for most cellular mRNA is reduced. Internal ribosomal entry increases in response to hypoxia, cell differentiation, apoptosis, gamma irradiation, and heat shock. Heat shock is the principal cellular stress in which general cap-dependent translation is inhibited. On the other hand, heat shock induces the preferential translation of a small class of mRNA, called heat shock protein (HSP) mRNAs, which probably occurs because little or no eIF4F activity is required for their translation. In this study, we found that continuous heat stress enhances expression of the heat shock protein BiP at the level of translation. Interestingly, heat stress also enhanced the viral IRES-dependent translation of encephalomyocarditis virus and hepatitis C virus but not poliovirus. Although several BiP inducers increased BiP protein expression, BiP IRES-dependent translation was enhanced only during heat shock, suggesting that heat shock is a specific inducer for BiP IRES-dependent translation. Taken together, these results indicate that the mechanism of IRES-dependent translation can be used during heat shock and suggest that this translational mechanism may be critical to the survival and proliferation of cells under stress.
authors.affiliation: NRL, Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology, San31, Hyoja-Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
mesh_terms: D020121:5' Untranslated Regions; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D015534:Trans-Activators; D008156:Luciferases