Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a novel mechanism in transcription control.

Nuclear FGFR1 acts as a developmental gene regulator in cooperation with FGF-2, RSK1, and CREB-binding protein (CBP). FRAP analysis revealed three nuclear FGFR1 populations: i) a fast mobile, ii) a slower mobile population reflecting chromatin-bound FGFR1, and iii) an immobile FGFR1 population associated with the nuclear matrix. Factors (cAMP, CBP) ...
that induce FGFR1-mediated gene activation shifted FGFR1 from the nuclear matrix (immobile) to chromatin (slow) and reduced the movement rate of the chromatin-bound population. Transcription inhibitors accelerated FGFR1 movement; the content of the chromatin-bound slow FGFR1 decreased, whereas the fast population increased. The transcriptional activation appears to involve conversion of the immobile matrix-bound and the fast nuclear FGFR1 into a slow chromatin-binding population through FGFR1's interaction with CBP, RSK1, and the high-molecular-weight form of FGF-2. Our findings support a general mechanism in which gene activation is governed by protein movement and collisions with other proteins and nuclear structures.
Mesh Terms:
Animals, CREB-Binding Protein, Cell Compartmentation, Cell Line, Cell Nucleus, Fibroblast Growth Factor 2, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, Humans, Mice, Models, Biological, Molecular Weight, Nuclear Matrix, Protein Binding, Protein Structure, Tertiary, Protein Transport, Receptor, Fibroblast Growth Factor, Type 1, Recombinant Fusion Proteins, Ribosomal Protein S6 Kinases, 90-kDa, Transcription, Genetic, Transcriptional Activation, Transfection
Mol. Biol. Cell
Date: May. 01, 2009
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