Fibroblast growth factor 3, a protein with a dual subcellular fate, is interacting with human ribosomal protein S2.
The secreted isoform of fibroblast growth factor 3 (FGF3) induces a mitogenic cell response, while the nuclear form inhibits cell proliferation. Recently, we identified a nucleolar FGF3-binding protein which is implicated in processing of pre-rRNA as a possible target of nuclear FGF3 signalling. Here, we report a second candidate protein identified by a yeast two-hybrid screen for nuclear FGF3 action, ribosomal protein S2, rpS2. Recombinant rpS2 binds to in vitro translated FGF3 and to nuclear FGF3 extracted from transfected COS-1 cells. Characterization of the FGF3 binding domain of rpS2 showed that both the Arg-Gly-rich N-terminal region and a short carboxyl-terminal sequence of rpS2 are necessary for FGF3 binding. Mapping the S2 binding domains of FGF3 revealed that these domains are important for both NoBP and rpS2 interaction. Transient co-expression of rpS2 and nuclear FGF3 resulted in a reduced nucleolar localization of the FGF. These findings suggest that the nuclear form of FGF3 inhibits cell proliferation by interfering with ribosomal biogenesis.
Antoine
Marianne
M
Institute of Clinical Chemistry and Pathobiochemistry, RWTH Aachen, Germany.
Reimers
Kerstin
K
Wirz
Werner
W
Gressner
Axel M
AM
Müller
Robert
R
Kiefer
Paul
P
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D051518:Fibroblast Growth Factor 3 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism*
D051518:Fibroblast Growth Factor 3; D012269:Ribosomal Proteins; C030004:ribosomal protein S2