FIBROBLAST GROWTH FACTOR-II (FGF-2) IN THE NUCLEUS - TRANSLOCATION PROCESS AND TARGETS

FGF-2 (basic fibroblast growth factor) was recently detected in the nu cleus of a variety of cell types. The large isoforms contain a functio nal nuclear localization signal that allows their nuclear accumulation in producing cells, while a small amount of FGF-2 added exogenously t o target cells is translocated to the nucleus in phase G1 of the cell cycle according to an unknown process. We report here using Chinese ha mster ovary cell mutants bearing deficiency in heparan sulfate proteog lycans (HSPGs) synthesis that HSPGs are required for transport of exog enous FGF-2 to the nucleus. Furthermore a co-transport was suggested s ince an active complex containing FGF-2 and HSPGs was isolated from nu clei of treated cells. Several FGF-2 nuclear targets were described. I n vivo as in vitro, it activates rDNA transcription and it binds to a specific DNA sequence that is present in the nontranscribed spacer of ribosomal genes. In vitro, FGF-2 has a strong affinity for histone H1 and it activates the protein kinase CKII. In the nucleus FGF-2 could r egulate gene expression through modulation of chromatin structure.