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 ce...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-04, Vol.274 (15), p.10382-10387
Main Authors: Ueba, T, Kaspar, B, Zhao, X, Gage, F H
Format: Article
Language:English
Subjects:
Alternative Splicing
Amino Acid Sequence
Cell Line
Cloning, Molecular
DNA - metabolism
DNA-Binding Proteins
Fibroblast Growth Factor 2 - genetics
Humans
Immunohistochemistry
Molecular Sequence Data
Repressor Proteins - chemistry
Repressor Proteins - genetics
Transcription Factors
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.15.10382