scholarly journals Alternative translation of human fibroblast growth factor 2 mRNA occurs by internal entry of ribosomes.

1995 ◽  
Vol 15 (1) ◽  
pp. 35-44 ◽  
Author(s):  
S Vagner ◽  
M C Gensac ◽  
A Maret ◽  
F Bayard ◽  
F Amalric ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Translation Initiation ◽  
Internal Ribosome Entry Site ◽  
Human Fibroblast ◽  
Untranslated Region ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Entry Site ◽  
Internal Ribosome Entry

Alternative initiations of translation of the human fibroblast growth factor 2 (FGF-2) mRNA, at three CUG start codons and one AUG start codon, result in the synthesis of four isoforms of FGF-2. This process has important consequences on the fate of FGF-2: the CUG-initiated products are nuclear and their constitutive expression is able to induce cell immortalization, whereas the AUG-initiated product, mostly cytoplasmic, can generate cell transformation. Thus, the different isoforms probably have distinct targets in the cell. We show here that translation initiation of the FGF-2 mRNA breaks the rule of the cap-dependent ribosome scanning mechanism. First, translation of the FGF-2 mRNA was shown to be cap independent in vitro. This cap-independent translation required a sequence located between nucleotides (nt) 192 and 256 from the 5' end of the 318-nt-long 5' untranslated region. Second, expression of bicistronic vectors in COS-7 cells indicated that the FGF-2 mRNA is translated through a process of internal ribosome entry mediated by the mRNA leader sequence. By introducing additional AUG codons into the RNA leader sequence, we localized an internal ribosome entry site to between nt 154 and 318 of the 5' untranslated region, just upstream of the first CUG. The presence of an internal ribosome entry site in the FGF-2 mRNA suggests that the process of internal translation initiation, by controlling the expression of a growth factor, could have a crucial role in the control of cell proliferation and differentiation.

scholarly journals Hyperglycemia upregulates translation of the fibroblast growth factor 2 mRNA in mouse aorta via internal ribosome entry site

2004 ◽  
Vol 18 (13) ◽  
pp. 1583-1585 ◽  
Author(s):  
Shigetada Teshima‐Kondo ◽  
Kazumi Kondo ◽  
Leonel Prado‐Lourenco ◽  
Irma Gabriela Gonzalez‐Herrera ◽  
Kazuhito Rokutan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Internal Ribosome Entry Site ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Mouse Aorta

scholarly journals p53 directs conformational change and translation initiation blockade of human fibroblast growth factor 2 mRNA

Oncogene ◽  
2001 ◽  
Vol 20 (34) ◽  
pp. 4613-4620 ◽  
Author(s):  
Bruno Galy ◽  
Laurent Créancier ◽  
Leonel Prado-Lourenço ◽  
Anne-Catherine Prats ◽  
Hervé Prats
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Conformational Change ◽  
Translation Initiation ◽  
Human Fibroblast ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth

scholarly journals Fibroblast Growth Factor 2 Internal Ribosome Entry Site (Ires) Activity Ex Vivo and in Transgenic Mice Reveals a Stringent Tissue-Specific Regulation

2000 ◽  
Vol 150 (1) ◽  
pp. 275-281 ◽  
Author(s):  
Laurent Créancier ◽  
Dominique Morello ◽  
Pascale Mercier ◽  
Anne-Catherine Prats
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Internal Ribosome Entry Site ◽  
Tissue Specificity ◽  
Ex Vivo ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Entry Site ◽  
Internal Ribosome Entry

Fibroblast growth factor 2 (FGF-2) is a powerful mitogen involved in proliferation, differentiation, and survival of various cells including neurons. FGF-2 expression is translationally regulated; in particular, the FGF-2 mRNA contains an internal ribosome entry site (IRES) allowing cap-independent translation. Here, we have analyzed FGF-2 IRES tissue specificity ex vivo and in vivo by using a dual luciferase bicistronic vector. This IRES was active in most transiently transfected human and nonhuman cell types, with a higher activity in p53 −/− osteosarcoma and neuroblastoma cell lines. Transgenic mice were generated using bicistronic transgenes with FGF-2 IRES or encephalomyocarditis virus (EMCV) IRES. Measurements of luciferase activity revealed high FGF-2 IRES activity in 11-d-old embryos (E11) but not in the placenta; activity was high in the heart and brain of E16. FGF-2 IRES activity was low in most organs of the adult, but exceptionally high in the brain. Such spatiotemporal variations were not observed with the EMCV IRES. These data, demonstrating the strong tissue specificity of a mammalian IRES in vivo, suggest a pivotal role of translational IRES- dependent activation of FGF-2 expression during embryogenesis and in adult brain. FGF-2 IRES could constitute, thus, a powerful tool for gene transfer in the central nervous system.

scholarly journals A New 34-Kilodalton Isoform of Human Fibroblast Growth Factor 2 Is Cap Dependently Synthesized by Using a Non-AUG Start Codon and Behaves as a Survival Factor

1999 ◽  
Vol 19 (1) ◽  
pp. 505-514 ◽  
Author(s):  
Emmanuelle Arnaud ◽  
Christian Touriol ◽  
Christel Boutonnet ◽  
Marie-Claire Gensac ◽  
Stéphan Vagner ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Human Fibroblast ◽  
The Other ◽  
In Vitro Translation ◽  
Start Codon ◽  
Fibroblast Growth Factor 2 ◽  
Initiation Codon ◽  
Fibroblast Growth

ABSTRACT Four isoforms of human fibroblast growth factor 2 (FGF-2) result from alternative initiations of translation at three CUG start codons and one AUG start codon. Here we characterize a new 34-kDa FGF-2 isoform whose expression is initiated at a fifth initiation codon. This 34-kDa FGF-2 was identified in HeLa cells by using an N-terminal directed antibody. Its initiation codon was identified by site-directed mutagenesis as being a CUG codon located at 86 nucleotides (nt) from the FGF-2 mRNA 5′ end. Both in vitro translation and COS-7 cell transfection using bicistronic RNAs demonstrated that the 34-kDa FGF-2 was exclusively expressed in a cap-dependent manner. This contrasted with the expression of the other FGF-2 isoforms of 18, 22, 22.5, and 24 kDa, which is controlled by an internal ribosome entry site (IRES). Strikingly, expression of the other FGF-2 isoforms became partly cap dependent in vitro in the presence of the 5,823-nt-long 3′ untranslated region of FGF-2 mRNA. Thus, the FGF-2 mRNA can be translated both by cap-dependent and IRES-driven mechanisms, the balance between these two mechanisms modulating the ratio of the different FGF-2 isoforms. The function of the new FGF-2 was also investigated. We found that the 34-kDa FGF-2, in contrast to the other isoforms, permitted NIH 3T3 cell survival in low-serum conditions. A new arginine-rich nuclear localization sequence (NLS) in the N-terminal region of the 34-kDa FGF-2 was characterized and found to be similar to the NLS of human immunodeficiency virus type 1 Rev protein. These data suggest that the function of the 34-kDa FGF-2 is mediated by nuclear targets.

scholarly journals Purification of the human fibroblast growth factor 2 using novel animal-component free materials

2020 ◽  
Vol 1626 ◽  
pp. 461367
Author(s):  
Svenja Nicolin Bolten ◽  
Anne-Sophie Knoll ◽  
Zhaopeng Li ◽  
Pia Gellermann ◽  
Iliyana Pepelanova ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Human Fibroblast ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Animal Component
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