IRES-dependent regulation of FGF-2 mRNA translation in pathophysiological conditions in the mouse
| Autor: | I G, Gonzalez-Herrera, L, Prado-Lourenco, S, Teshima-Kondo, K, Kondo, F, Cabon, J-F, Arnal, F, Bayard, A-C, Prats |
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| Přispěvatelé: | Hormones, facteurs de croissance et physiopathologie vasculaire, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), MilleGen, Prologue Biotech, Department of nutrition, Tokushima University, Oncogénèse, différenciation et transduction du signal (ODTS), IFR89-Centre National de la Recherche Scientifique (CNRS), Harel-Bellan, Annick |
| Rok vydání: | 2006 |
| Předmět: |
MESH: Peptide Chain Initiation
Translational MESH: Diabetes Mellitus MESH: Mice Transgenic MESH: Codon Initiator Codon Initiator Mice Transgenic Biochemistry Mice Diabetes Mellitus [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals MESH: Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Peptide Chain Initiation Translational MESH: Mice MESH: Fibroblast Growth Factor 2 fungi MESH: Blood Vessels MESH: Gene Expression Regulation Gene Expression Regulation Protein Biosynthesis MESH: Protein Biosynthesis Blood Vessels Fibroblast Growth Factor 2 Ribosomes MESH: Ribosomes |
| Zdroj: | Biochem Soc Trans Biochem Soc Trans, 2006, 34, pp.17-21. ⟨10.1042/BST20060017⟩ |
| ISSN: | 1470-8752 0300-5127 |
| DOI: | 10.1042/bst0340017 |
| Popis: | The mRNA coding for FGF-2 (fibroblast growth factor 2), a major angiogenic factor, is translated by an IRES (internal ribosome entry site)-dependent mechanism. We have studied the role of the IRES in the regulation of FGF-2 expression in vivo, under pathophysiological conditions, by creating transgenic mice lines expressing bioluminescent bicistronic transgenes. Analysis of FGF-2 IRES activity indicates strong tissue specificity in adult brain and testis, suggesting a role of the IRES in the activation of FGF-2 expression in testis maturation and brain function. We have explored translational control of FGF-2 mRNA under diabetic hyperglycaemic conditions, as FGF-2 is implied in diabetes-related vascular complications. FGF-2 IRES is specifically activated in the aorta wall in streptozotocin-induced diabetic mice, in correlation with increased expression of endogenous FGF-2. Thus, under hyperglycaemic conditions, where cap-dependent translation is blocked, IRES activation participates in FGF-2 overexpression, which is one of the keys of diabetes-linked atherosclerosis aggravation. IRES activation under such pathophysiological conditions may involve ITAFs (IRES trans-acting factors), such as p53 or hnRNP AI (heterogeneous nuclear ribonucleoprotein AI), recently identified as inhibitory or activatory ITAFs respectively for FGF-2 IRES. |
| Databáze: | OpenAIRE |
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