Involvement of Basic Fibroblast Growth Factor NH2 Terminus in Nuclear Accumulation

AbstractThe human basic Fibroblast Growth Factor (bFGF) gene was shown to encode four polypeptides by an alternative use of initiation codons (three CUG and one AUG). In this report, we present a comparative study of the fate and intracellular localization of individual bFGF isoforms. For this purpose, we have produced the various bFGF isoforms in E. coli and purified them to homogeneity, the 210 amino acid form initiated at CUG1 that contains a nuclear localization sequence (NLS), the 155 amino acid form (AUG-mediated initiation) and the 146 amino acid form (processed form extracted from tissues). While the different bFGFs were taken up by the cell with equal efficiency, more of the 210 amino acid form accumulated in the nucleus and represented 36% of the internalized bFGF compared with 15% in the others. A chimeric protein containing the minimal SV40 Large T NLS (SV40NLS) fused to the 155 amino acid bFGF form (SVbFGF) behaves like the native 155 amino acid form, indicating that nuclear accumulation of e...