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Mol Cell Biol. 2005 Nov;25(21):9419-26.

Direct regulation of rRNA transcription by fibroblast growth factor 2.

Author information

1
Molecular and Cellular Biology Program, State University of New York, Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203, USA.

Abstract

Fibroblast growth factor 2 (FGF-2), which is highly expressed in developing tissues and malignant cells, regulates cell growth, differentiation, and migration. Five isoforms (18 to approximately 34 kDa) of FGF-2 are derived from alternative initiation codons of a single mRNA. The 18-kDa FGF-2 isoform is released from cells by a nonclassical secretory pathway and regulates gene expression by binding to cell surface receptors. This isoform also localizes to the nucleolus, raising the possibility that it may directly regulate ribosome biogenesis, a rate-limiting process in cell growth. Although several growth factors have been shown to accumulate in the nucleolus, their function and mechanism of action remain unclear. Here we show that 18-kDa FGF-2 interacts with upstream binding factor (UBF), an architectural transcription factor essential for rRNA transcription. The maximal activation of rRNA transcription in vitro by 18-kDa FGF-2 requires UBF. The 18-kDa FGF-2 localizes to rRNA genes and is necessary for the full activation of pre-rRNA synthesis in vivo. Our results demonstrate that 18-kDa FGF-2 directly regulates rRNA transcription.

PMID:
16227592
PMCID:
PMC1265826
DOI:
10.1128/MCB.25.21.9419-9426.2005
[Indexed for MEDLINE]
Free PMC Article

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