title: Permeable FGF-1 nuclear localization signal peptide stimulates DNA synthesis in various cell types but is cell-density sensitive and unable to support cell proliferation.
abstract: An earlier report indicated that a 26-amino-acid peptide (SA), comprised of the nuclear localization signal (NLS) of fibroblast growth factor-1 (FGF-1) and a membrane-permeable peptide, was able to stimulate DNA synthesis after it was taken up by NIH3T3 fibroblasts. Here, we report that SA, but not a mutant with the NLS motif destroyed, induced DNA synthesis in BALB/c3T3 murine fibroblasts, human vascular endothelial (HUVE) cells, and primary cultured hepatocytes, although the activity was weaker than that of FGF-1. The kinetics of SA-induced DNA synthesis and G1 cyclin expression were similar to those elicited by FGF-1, indicating that SA induces cell cycle progression. Kinetic analysis also suggested that SA stimulates only a fraction of the DNA replication in BALB/c3T3 cells. At high cell densities, SA-induced G1 cyclin expression and DNA synthesis were more strongly inhibited than those induced by FGF-1. SA did not induce cell division in HUVE and BALB/c3T3 cells and did not interfere with FGF-1-stimulated proliferation of HUVE cells. These results indicate that SA is able to partially induce cell cycle progression through a contact-inhibition sensitive signaling pathway, but it is insufficient to support cell mitosis. We also suggest that signaling by SA does not interfere with that of FGF-1.
authors.affiliation: Biosignaling Department, National Institute of Bioscience and Human Technology, 1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Komi
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Imamura
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002460:Cell Line; D002463:Cell Membrane Permeability; D019938:Cyclin D1 / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis*; D004730:Endothelium, Vascular; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology
chemical_list: D008934:Mitogens; D019913:Nuclear Localization Signals; D010446:Peptide Fragments; D019938:Cyclin D1; D005346:Fibroblast Growth Factors; D004247:DNA