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Molecular and Cellular Biology, January 1999, p. 505-514, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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
Emmanuelle
Arnaud,
Christian
Touriol,
Christel
Boutonnet,
Marie-Claire
Gensac,
Stéphan
Vagner,
Hervé
Prats, and
Anne-Catherine
Prats*
INSERM U397, Endocrinologie et Communication
Cellulaire, Institut Louis Bugnard, C.H.U. Rangueil, 31403 Toulouse
Cedex 04, France
Received 30 July 1998/Returned for modification 28 September
1998/Accepted 15 October 1998
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.
*
Corresponding author. Mailing address: INSERM U397,
Endocrinologie et Communication Cellulaire, Institut Louis Bugnard,
C.H.U. Rangueil, Avenue Jean Poulhès, 31403 Toulouse Cedex 04, France. Phone: 33 (5) 61 32 21 42. Fax: 33 (5) 61 32 21 41. E-mail:
pratsac{at}rangueil.inserm.fr.

Present address: Swiss Institute for Experimental Cancer Research,
1066 Epalinges,
Switzerland.
Molecular and Cellular Biology, January 1999, p. 505-514, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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