Lang, K.Kappel, A.Goodall, G.Wickens, M.P.2006-06-262006-06-262002Molecular Biology of the Cell, 2002; 13(5):1792-18011059-15241939-4586http://hdl.handle.net/2440/9694Copyright © 2002 by The American Society for Cell BiologyHIF-1α is the regulated subunit of the HIF-1 transcription factor, which induces transcription of a number of genes involved in the cellular response to hypoxia. The HIF-1α protein is rapidly degraded in cells supplied with adequate oxygen but is stabilized in hypoxic cells. Using polysome profile analysis, we found that translation of HIF-1α mRNA in NIH3T3 cells is spared the general reduction in translation rate that occurs during hypoxia. To assess whether the 5'UTR of the HIF-1α mRNA contains an internal ribosome entry site (IRES), we constructed a dicistronic reporter with the HIF-1α 5'UTR inserted between two reporter coding regions. We found that the HIF-1α 5'UTR promoted translation of the downstream reporter, indicating the presence of an IRES. The IRES had activity comparable to that of the well-characterized c-myc IRES. IRES activity was not affected by hypoxic conditions that caused a reduction in cap-dependent translation, and IRES activity was less affected by serum-starvation than was cap-dependent translation. These data indicate that the presence of an IRES in the HIF-1α 5'UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation.enHela Cells3T3 CellsRibosomesAnimalsHumansMiceOxygenIntercellular Signaling Peptides and ProteinsVascular Endothelial Growth FactorsVascular Endothelial Growth Factor AEndothelial Growth FactorsTranscription FactorsRNA, Messenger5' Untranslated RegionsLymphokinesCulture Media, Serum-FreeProtein BiosynthesisGenes, mycHypoxia-Inducible Factor 1, alpha SubunitHypoxiaJournal article002002048010.1091/mbc.02-02-00170001758129000282-s2.0-003600002860365Goodall, G. [0000-0003-1294-0692]