Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor.

TLDR

The study investigated the subcellular localization of bFGF variants produced from alternative translation initiation sites. They expressed bFGF variants in COS cells and used chimeric bFGF–CAT constructs to determine localization. AUG‑initiated bFGF localizes to the cytoplasm, whereas CUG‑initiated forms localize to the nucleus, with a 37‑residue signal sequence between the second CUG and AUG mediating nuclear import, indicating that alternative initiation controls bFGF subcellular localization and potentially its growth‑regulatory functions.

Abstract

Three forms of basic fibroblast growth factor (bFGF), initiated at an AUG (18 kDa) and two CUG (21 and 22.5 kDa) start codons, were produced following transfection of COS cells with human hepatoma bFGF cDNA. The subcellular localization of the different forms was investigated directly or by using chimeric genes constructed by fusion of the bFGF and chloramphenicol acetyltransferase open reading frames. The AUG-initiated proteins were cytoplasmic, while the CUG-initiated forms were nuclear. The signal sequence responsible for the nuclear localization of bFGF is contained within 37 amino acid residues between the second CUG and the AUG start codons. Alternative initiation of translation regulates the subcellular localization of bFGF and thus could modulate its role in cell growth and differentiation control.