Nucleolar association of fibroblast growth factor 3 via specific sequence motifs has inhibitory effects on cell growth
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| Published in | Molecular and Cellular Biology Vol. 15; no. 8; pp. 4364 - 4374 |
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| Format | Journal Article |
| Language | English |
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United States
American Society for Microbiology
01.08.1995
Taylor & Francis |
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The dual subcellular fate of fibroblast growth factor 3 (FGF3) is determined by the competing effects of amino-terminal signals for nuclear localization and secretion. Mutation analysis has implicated additional basic domains in the carboxy-terminal region of the protein as necessary for nuclear uptake and the association of FGF3 with the nucleoli. Immunogold electron microscopy shows that FGF3 is predominantly within the dense fibrillar component of the nucleolus. A form of FGF3 that localizes exclusively in the nucleus and nucleolus was generated by removing signals for secretion, and expression of this nonsecreted FGF3 in a mammary epithelial cell line resulted in slowly growing colonies of enlarged cells. Thus, nuclear import and nucleolar association of FGF3 are determined by the concerted interaction of several distinct motifs, and the exclusive production of the nuclear isoform can inhibit DNA synthesis and cell proliferation. The dual subcellular fate of fibroblast growth factor 3 (FGF3) is determined by the competing effects of amino-terminal signals for nuclear localization and secretion (P. Kiefer, P. Acland, D. Pappin, G. Peters, and C. Dickson, EMBO J. 13:4126-4136, 1994). Mutation analysis has implicated additional basic domains in the carboxy-terminal region of the protein as necessary for nuclear uptake and the association of FGF3 with the nucleoli. Immunogold electron microscopy shows that FGF3 is predominantly within the dense fibrillar component of the nucleolus. A form of FGF3 that localizes exclusively in the nucleus and nucleolus was generated by removing signals for secretion, and expression of this nonsecreted FGF3 in a mammary epithelial cell line resulted in slowly growing colonies of enlarged cells. Thus, nuclear import and nucleolar association of FGF3 are determined by the concerted interaction of several distinct motifs, and the exclusive production of the nuclear isoform can inhibit DNA synthesis and cell proliferation. |
| Author | C Dickson P Kiefer |
| AuthorAffiliation | Imperial Cancer Research Fund, London, United Kingdom |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/7623831$$D View this record in MEDLINE/PubMed |
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| References | Peters G. (bib35) 1991; 2 bib14 bib36 bib15 bib37 bib10 Hatanaka M. (bib18) 1990; 12 bib32 bib11 bib33 bib31 Kiefer P. (bib24) 1993; 13 bib27 bib28 Dixon M. (bib13) 1989; 9 Goldfarb M. (bib17) 1990; 1 Stamp G. (bib43) 1992; 3 bib40 Mathieu M. (bib29) 1995; 270 Dickson C. (bib12) 1989; 1 bib25 bib47 bib26 bib23 bib45 Fuller-Pace F. (bib16) 1991; 115 bib46 bib21 bib22 bib44 bib41 bib20 bib28a bib42 bib9 bib7 bib8 bib5 Messmer B. (bib30) 1993; 161 bib6 bib19 Ornitz D. (bib34) 1992; 84 bib3 bib38 bib4 bib39 bib1 bib2 |
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Mendeley... The dual subcellular fate of fibroblast growth factor 3 (FGF3) is determined by the competing effects of amino-terminal signals for nuclear localization and... |
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| SubjectTerms | Amino Acid Sequence Animals Biological Transport Cell Compartmentation Cell Division - drug effects Cell Nucleolus - metabolism Cell Nucleolus - ultrastructure Cells, Cultured Clone Cells DNA - biosynthesis DNA Mutational Analysis Fibroblast Growth Factors - genetics Fibroblast Growth Factors - metabolism Fibroblast Growth Factors - pharmacology Fluorescent Antibody Technique Growth Inhibitors - genetics Growth Inhibitors - metabolism Growth Inhibitors - pharmacology Microscopy, Immunoelectron Molecular Sequence Data Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins - pharmacology Recombinant Proteins - metabolism Structure-Activity Relationship Transfection |
| Title | Nucleolar association of fibroblast growth factor 3 via specific sequence motifs has inhibitory effects on cell growth |
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