| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Institut National de la Santé et la Recherche Médicale Unité 397, Endocrinologie et Communication Cellulaire, Institut Fédératif de Recherche Louis Bugnard, Centre Hospitalier Universitaire Rangueil, 31403 Toulouse cedex 04, France
We recently demonstrated that the very long 5'-untranslated region (5'-UTR) of the vascular endothelial growth factor (VEGF) mRNA contains two independent internal ribosome entry sites (IRES A and B). In the human sequence, four potential CUG translation initiation codons are located in between these IRES and are in frame with the classical AUG start codon. By in vitro translation and COS-7 cell transfections, we demonstrate that a high mol wt VEGF isoform [called large VEGF (L-VEGF)] is generated by an alternative translation initiation process, which occurs at the first of these CUG codons. Using a bicistronic strategy, we show that the upstream IRES B controls the translation initiation of L-VEGF. This isoform is 206 amino acids longer than the classical AUG-initiated form. With a specific antibody raised against this NH2 extension, we show that the L-VEGF is present in different mouse tissues or in transfected COS-7 cells. We also demonstrate that L-VEGF is cleaved into two fragments: a 23-kDa NH2-specific fragment and a fragment with an apparent size similar to that of the classical AUG-initiated form. This cleavage requires the integrity of a hydrophobic sequence located in the central part of the L-VEGF molecule. This sequence actually plays the role of signal peptide in the classical AUG-initiated form. The AUG-initiated form and the COOH cleavage product of the L-VEGF are both secreted. In contrast, the large isoform and its NH2 fragment present an intracellular localization.
These data unravel a further level of complexity in the regulation of VEGF expression.
This article has been cited by other articles:
 |
|
 |
|
  R. M. Young, S.-J. Wang, J. D. Gordan, X. Ji, S. A. Liebhaber, and M. C. Simon Hypoxia-mediated Selective mRNA Translation by an Internal Ribosome Entry Site-independent Mechanism J. Biol. Chem., June 13, 2008; 283(24): 16309 - 16319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Shinohara, H.-J. Kim, J.-H. Kim, V. A. Garcia, and H. Cantor Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells PNAS, May 20, 2008; 105(20): 7235 - 7239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bastide, Z. Karaa, S. Bornes, C. Hieblot, E. Lacazette, H. Prats, and C. Touriol An upstream open reading frame within an IRES controls expression of a specific VEGF-A isoform Nucleic Acids Res., April 1, 2008; 36(7): 2434 - 2445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bornes, L. Prado-Lourenco, A. Bastide, C. Zanibellato, J. S. Iacovoni, E. Lacazette, A.-C. Prats, C. Touriol, and H. Prats Translational Induction of VEGF Internal Ribosome Entry Site Elements During the Early Response to Ischemic Stress Circ. Res., February 16, 2007; 100(3): 305 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. I.V. Errera, L. H. Canani, M. E. R. Silva, E. Yeh, W. Takahashi, K. G. Santos, K. E.P. Souto, B. Tschiedel, I. Roisenberg, J. L. Gross, et al. Functional Vascular Endothelial Growth Factor -634G>C SNP Is Associated With Proliferative Diabetic Retinopathy: A case-control study in a Brazilian population of European ancestry Diabetes Care, February 1, 2007; 30(2): 275 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Baird, M. Turcotte, R. G. Korneluk, and M. Holcik Searching for IRES RNA, October 1, 2006; 12(10): 1755 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Plotkin and M. S. Goligorsky Mesenchymal cells from adult kidney support angiogenesis and differentiate into multiple interstitial cell types including erythropoietin-producing fibroblasts Am J Physiol Renal Physiol, October 1, 2006; 291(4): F902 - F912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Summers, B. M. Coupes, M. F. Brennan, S. A. Ralph, C. D. Short, and P. E. C. Brenchley VEGF -460 genotype plays an important role in progression to chronic kidney disease stage 5 Nephrol. Dial. Transplant., November 1, 2005; 20(11): 2427 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Thomson, C. M. Cahill, H.-H. Cho, K. D. Kassachau, M. R. Epis, K. R. Bridges, P. J. Leedman, and J. T. Rogers The Acute Box cis-Element in Human Heavy Ferritin mRNA 5'-Untranslated Region Is a Unique Translation Enhancer That Binds Poly(C)-binding Proteins J. Biol. Chem., August 26, 2005; 280(34): 30032 - 30045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Jang, L. E.-C. Leong, L. T. Hoang, P. H. Wang, G. A. Gutman, and B. L. Semler Structurally Distinct Elements Mediate Internal Ribosome Entry within the 5'-Noncoding Region of a Voltage-gated Potassium Channel mRNA J. Biol. Chem., November 12, 2004; 279(46): 47419 - 47430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Woolard, W.-Y. Wang, H. S. Bevan, Y. Qiu, L. Morbidelli, R. O. Pritchard-Jones, T.-G. Cui, M. Sugiono, E. Waine, R. Perrin, et al. VEGF165b, an Inhibitory Vascular Endothelial Growth Factor Splice Variant: Mechanism of Action, In vivo Effect On Angiogenesis and Endogenous Protein Expression Cancer Res., November 1, 2004; 64(21): 7822 - 7835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bossard, L. V. d. Berghe, H. Laurell, C. Castano, M. Cerutti, A.-C. Prats, and H. Prats Antiangiogenic Properties of Fibstatin, an Extracellular FGF-2-Binding Polypeptide Cancer Res., October 15, 2004; 64(20): 7507 - 7512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Segrelles, S. Ruiz, M. Santos, J. Martinez-Palacio, M. F. Lara, and J. M. Paramio Akt mediates an angiogenic switch in transformed keratinocytes Carcinogenesis, July 1, 2004; 25(7): 1137 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bornes, M. Boulard, C. Hieblot, C. Zanibellato, J. S. Iacovoni, H. Prats, and C. Touriol Control of the Vascular Endothelial Growth Factor Internal Ribosome Entry Site (IRES) Activity and Translation Initiation by Alternatively Spliced Coding Sequences J. Biol. Chem., April 30, 2004; 279(18): 18717 - 18726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Miles, J. Slight, L. Spraggon, M. O'Sullivan, C. Patek, and N. D. Hastie Mice Lacking the 68-Amino-Acid, Mammal-Specific N-Terminal Extension of WT1 Develop Normally and Are Fertile Mol. Cell. Biol., April 1, 2003; 23(7): 2608 - 2613. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
