Previous Article | Next Article ![]()
Molecular and Cellular Biology, August 2001, p. 4996-5007, Vol. 21, No. 15
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
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

-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.
Present address: Ruhr-Universität Bochum, Institut für
Pharmakologie, D-44780 Bochum, Germany.
This article has been cited by other articles:
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»