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| 16 July 1998, Volume 17, Number 2, Pages 227-236 |
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| Article |
| Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription |
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| Gal Akiri1, Dorit Nahari1, Yiftach Finkelstein1, Shu-Yun Le2, Orna Elroy-Stein3,b and Ben-Zion Levi1,a,b |
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1Department of Food Engineering and Biotechnology, Technion, Haifa 32000, Israel
2The Laboratory of Experimental and Computational Biology, DBS, NCI, NIH, Frederick, Maryland 21702, USA
3Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel
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aAuthor for correspondence bO Elroy-Stein and B-Z Levi equally directed this research |
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| Abstract |
| Vascular Endothelial Growth Factor (VEGF) is a very potent angiogenic agent that has a central role in normal physiological angiogenesis as well as in tumor angiogenesis. VEGF expression is induced by hypoxia and hypoglycemia, and thus was suggested to promote neovascularization during tumor outgrowth. Yet, the molecular mechanism that governs VEGF expression is not fully characterized. VEGF induction is attributed in part to increased levels of transcription and RNA stability. Previously, we demonstrated that the 5' Untranslated Region (5' UTR) of VEGF has an important regulatory role in its expression. VEGF has an exceptionally long 5' UTR (1038 bp) which is highly rich in G+C nucleotides. This suggests that secondary structures in the 5' UTR might be essential for VEGF expression through transcriptional and post-transcriptional control mechanisms, as demonstrated for other growth factors. In this communication, we provide evidence that a computer predicted Internal Ribosome Entry Site (IRES) structure is biologically active and is located at the 3' end of the UTR. In addition, the results demonstrate that an alternative transcriptional initiation site for VEGF exists in the 5' UTR of VEGF. This alternative initiation site is 633 bp downstream of the main transcription start site and the resulting 5' UTR includes mainly the IRES structure. Therefore, our results suggest that VEGF is subjected to regulation at either translational level through a mechanism of ribosome internal initiation and/or transcriptional level through alternative initiation. |
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| Keywords |
| vascular endothelial growth factor (VEGF); internal ribosome entry site (IRES); 5' untranslated region; translational regulation; angiogenesis |
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| Received 14 January 1998; revised 31 March 1998; accepted 31 March 1998 |
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| 16 July 1998, Volume 17, Number 2, Pages 227-236 |
| Table of contents Previous Abstract Next Article PDF |
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