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NoBP, a nuclear fibroblast growth factor 3 binding protein, is cell cycle regulated and promotes cell growth
K Reimers1, M Antoine, M Zapatka
1Institut für Hämostaseologie und Transfusionsmedizin, Medizinische Fakultät, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany.
Abstract:
Secreted and nuclear forms of fibroblast growth factor 3 (FGF3) have opposing effects on cells. The secreted form stimulates cell growth and transformation, while the nuclear form inhibits DNA synthesis and cell proliferation. By using the yeast two-hybrid system we have identified a nucleolar FGF3 binding protein (NoBP) which coimmunoprecipitated and colocalized with FGF3 in transfected COS-1 cells. Characterization of the NoBP binding domain of FGF3 exactly matched the sequence requirements of FGF3 for its translocation into the nucleoli, suggesting that NoBP might be the nucleolar binding partner of FGF3 essential for its nucleolus localization. Carboxyl-terminal domains of NoBP contain linear nuclear and nucleolar targeting motifs which are capable of directing a heterologous protein beta-galactosidase to the nucleus and the nucleoli. While NoBP expression was detected in all analyzed proliferating established cell lines, NoBP transcription was rapidly downregulated in the promyelocytic leukemia cell line HL60 when induced to differentiate. Analysis on the expression pattern of NoBP mRNA throughout the cell cycle in HeLa cells synchronized by lovastatin demonstrated a substantial upregulation during the late G(1)/early S phase. NoBP overexpression conferred a proliferating effect onto NIH 3T3 cells and can counteract the inhibitory effect of nuclear FGF3, suggesting a role of NoBP in controlling proliferation in cells. We propose that NoBP is the functional target of nuclear FGF3 action.
Insights
Researchers identified a nucleolar FGF3 binding protein (NoBP) that interacts with fibroblast growth factor 3 (FGF3). NoBP plays a role in cell proliferation and may be the target of nuclear FGF3 action.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Fibroblast growth factor 3 (FGF3) exhibits dual functions: secreted FGF3 promotes cell growth, while nuclear FGF3 inhibits proliferation.
- Understanding the molecular mechanisms governing FGF3's nuclear functions is crucial for deciphering its role in cell cycle regulation.
Purpose of the Study:
- To identify and characterize the nucleolar binding partner of fibroblast growth factor 3 (FGF3).
- To elucidate the role of this binding partner in FGF3-mediated cellular effects and cell proliferation.
Main Methods:
- Yeast two-hybrid system for protein interaction screening.
- Co-immunoprecipitation and immunofluorescence to confirm protein interaction and localization.
- Analysis of NoBP mRNA expression during cell differentiation and cell cycle progression.
Main Results:
- Identified a nucleolar FGF3 binding protein (NoBP) that interacts with and co-localizes with FGF3 in the nucleoli.
- NoBP contains nuclear and nucleolar localization signals, directing proteins to these cellular compartments.
- NoBP expression is linked to proliferation and is downregulated during differentiation; its mRNA is upregulated during late G1/early S phase.
- NoBP overexpression promotes cell proliferation and counteracts the inhibitory effects of nuclear FGF3.
Conclusions:
- NoBP is a novel nucleolar binding partner of FGF3, essential for its nucleolar localization.
- NoBP plays a significant role in controlling cell proliferation and may mediate the effects of nuclear FGF3.
- NoBP represents a potential therapeutic target for modulating cell proliferation in diseases like cancer.