Repression of human fibroblast growth factor 2 by a novel transcription factor.
Here we describe the cloning of the regulator of fibroblast growth factor 2 (FGF-2) transcription (RFT) using a yeast one-hybrid screening with a defined motif in FGF-2 promoter as a target sequence. Overexpression of human RFT (RFT-A) reduces FGF-2 RNA and protein levels in both normal and tumor cell lines. Its splice variants, RFT-A' and RFT-B, have deletions in the putative DNA binding domain and fail to bind FGF-2 promoter and repress FGF-2 gene expression. The ratios of RFT isoforms differ between normal and tumor cells, with the splice variants dominating in tumor cells. Overexpression of RFT-A induces glioma cell death. Our data suggest that regulation of FGF-2 by RFT is important for cellular functions and may be impaired in certain tumors.
Ueba
T
T
Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Kaspar
B
B
Zhao
X
X
Gage
F H
FH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C066141:MBD1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D004247:DNA