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Molecular and Cellular Biology, August 2001, p. 4996-5007, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.4996-5007.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

NoBP, a Nuclear Fibroblast Growth Factor 3 Binding Protein, Is Cell Cycle Regulated and Promotes Cell Growth

Kerstin Reimers,1,dagger Marianne Antoine,1 Marcus Zapatka,1 Volker Blecken,1 Clive Dickson,2 and Paul Kiefer1,*

Institut für Hämostaseologie und Transfusionsmedizin, Medizinische Fakultät, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany,1 and Imperial Cancer Research Fund Laboratories, London WC2A 3PX, United Kingdom2

Received 14 November 2000/Returned for modification 21 December 2000/Accepted 26 April 2001

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 G1/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.


* Corresponding author. Mailing address: Heinrich-Heine-Universität, Medizinische Fakultat, Institut für Hämostaseologie und Transfusionsmedizin, Moorenstrasse 5, D-40225 Düsseldorf, Germany. Phone: 49-211-811-7344. Fax: 49-211-811-6649. E-mail: kiefer{at}med.uni-duesseldorf.de.

dagger Present address: Ruhr-Universität Bochum, Institut für Pharmakologie, D-44780 Bochum, Germany.


Molecular and Cellular Biology, August 2001, p. 4996-5007, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.4996-5007.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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