Direct regulation of rRNA transcription by fibroblast growth factor 2.
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.
Sheng
Zhi
Z
Molecular and Cellular Biology Program, State University of New York, Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203, USA.
Liang
Yanping
Y
Lin
Chih-Yin
CY
Comai
Lucio
L
Chirico
William J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D020459:Genes, rRNA; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D035463:Pol1 Transcription Initiation Complex Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D035463:Pol1 Transcription Initiation Complex Proteins; D020033:Protein Isoforms; D012322:RNA Precursors; D012335:RNA, Ribosomal; D011993:Recombinant Fusion Proteins; C063844:transcription factor UBF; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins