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Bruns AF, van Bergeijk J, Lorbeer C, Nolle A, Jungnickel J, Grothe C, Claus P: Fibroblast growth factor-2 regulates the stability of nuclear bodies. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12747-52. Epub 2009 Jul 17.
Nuclear bodies are distinct subnuclear structures. The survival of motoneuron (SMN) gene is mutated or deleted in patients with the neurodegenerative disease spinal muscular atrophy (SMA). The gene product SMN is a marker protein for one class of nuclear bodies denoted as nuclear gems. SMN has also been found in Cajal bodies, which co-localize with gems in many cell types. Interestingly, SMA patients display a reduced number of gems. Little is known about the regulation of nuclear body formation and stabilization. We have previously shown that a nuclear isoform of the fibroblast growth factor-2 (FGF-2 (23)) binds directly to SMN. In this study, we analyzed the consequences of FGF-2 (23) binding to SMN with regard to nuclear body formation. On a molecular level, we showed that FGF-2 (23) competed with Gemin2 (a component of the SMN complex that is necessary for gem stabilization) for binding to SMN. Down-regulation of Gemin2 by siRNA caused destabilization of SMN-positive nuclear bodies. This process is reflected in both cellular and in vivo systems by a negative regulatory function of FGF-2 in nuclear body formation: in HEK293 cells, FGF-2 (23) decreased the number of SMN-positive nuclear bodies. The same effect could be observed in motoneurons of FGF-2 transgenic mice. This study demonstrates the functional role of a growth factor in the regulation of structural entities of the nucleus. |
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