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Molecular and Cellular Biology, November 2005, p. 9419-9426, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9419-9426.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Direct Regulation of rRNA Transcription by Fibroblast Growth Factor 2

Molecular and Cellular Biology Program, School of Graduate Studies,¹ Department of Anatomy & Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203,² Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033³

Received 26 May 2005/ Returned for modification 17 June 2005/ Accepted 14 August 2005

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 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.

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