%0 Journal Article %1 Stein.1998 %A Stein, I. %A Itin, A. %A Einat, P. %A Skaliter, R. %A Grossman, Z. %A Keshet, E. %D 1998 %J Mol.Cell Biol. %K 3T3 A Animals Biosynthesis Cell Cells Cultured Endothelial Factor Factors Growth Humans Hypoxia Lymphokines Messenger Mice Neovascularization Oxygen Pathologic Protein RNA Rats Research Ribosomes Vascular biosynthesis cells genetics identify metabolism protein %N 6 %P 3112-3119 %T Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia %U PM:9584152 %V 18 %X Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic growth factor that promotes compensatory angiogenesis in circumstances of oxygen shortage. The requirement for translational regulation of VEGF is imposed by the cumbersome structure of the 5' untranslated region (5'UTR), which is incompatible with efficient translation by ribosomal scanning, and by the physiologic requirement for maximal VEGF production under conditions of hypoxia, where overall protein synthesis is compromised. Using bicistronic reporter gene constructs, we show that the 1,014-bp 5'UTR of VEGF contains a functional internal ribosome entry site (IRES). Efficient cap-independent translation is maintained under hypoxia, thereby securing efficient production of VEGF even under unfavorable stress conditions. To identify sequences within the 5'UTR required for maximal IRES activity, deletion mutants were analyzed. Elimination of the majority (851 nucleotides) of internal 5'UTR sequences not only ma

@article{Stein.1998, abstract = {Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic growth factor that promotes compensatory angiogenesis in circumstances of oxygen shortage. The requirement for translational regulation of VEGF is imposed by the cumbersome structure of the 5' untranslated region (5'UTR), which is incompatible with efficient translation by ribosomal scanning, and by the physiologic requirement for maximal VEGF production under conditions of hypoxia, where overall protein synthesis is compromised. Using bicistronic reporter gene constructs, we show that the 1,014-bp 5'UTR of VEGF contains a functional internal ribosome entry site (IRES). Efficient cap-independent translation is maintained under hypoxia, thereby securing efficient production of VEGF even under unfavorable stress conditions. To identify sequences within the 5'UTR required for maximal IRES activity, deletion mutants were analyzed. Elimination of the majority (851 nucleotides) of internal 5'UTR sequences not only ma}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Stein, I. and Itin, A. and Einat, P. and Skaliter, R. and Grossman, Z. and Keshet, E.}, biburl = {https://www.bibsonomy.org/bibtex/2f1617eb01949e0582f5e978630f47796/kanefendt}, interhash = {ec48976c80f5f72248ba852fcb9c45a8}, intrahash = {f1617eb01949e0582f5e978630f47796}, journal = {Mol.Cell Biol.}, keywords = {3T3 A Animals Biosynthesis Cell Cells Cultured Endothelial Factor Factors Growth Humans Hypoxia Lymphokines Messenger Mice Neovascularization Oxygen Pathologic Protein RNA Rats Research Ribosomes Vascular biosynthesis cells genetics identify metabolism protein}, number = 6, pages = {3112-3119}, timestamp = {2010-02-05T11:28:47.000+0100}, title = {Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia}, url = {PM:9584152}, volume = 18, year = 1998 }