TG-interacting factor (TGIF) is a transcriptional co-repressor that directly associates with Smad (Sma- and Mad-related protein) proteins and inhibits Smad-mediated transcriptional activation. By using Affymetrix (Santa Clara, CA, U.S.A.) oligonucleotide microarray analysis, we found that TGIF mRNA level was elevated by transforming-growth-factor-β (TGF-β) treatment in a human T-cell line, HuT78. Subsequent reverse-transcription PCR assays indicated that TGF-β1 and activin were able to induce a rapid and transient increase in the level of TGIF in both HuT78 and HepG2 hepatoma cells. To analyse whether or not the regulation of TGIF mRNA occurs at the transcriptional level, a 2.4kb human TGIF promoter was isolated. A primer extension assay was performed to localize the putative transcription initiation site of the promoter. When transiently expressed in HepG2 cells, this promoter was stimulated by TGF-β1 and activin treatment in a time-dependent manner. A series of deletion mutants of the TGIF promoter were also generated to further characterize the TGF-β responsive region of the promoter. In addition, expression of TGIF was able to cause a dose-dependent inhibition of TGF-β and activin signalling. Taken together, these experiments indicated that TGIF is a novel transcriptional target of TGF-β and activin signalling and is likely involved in a negative feedback loop to desensitize TGF-β/activin action.
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April 2003
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Research Article|
April 15 2003
Regulation of TG-interacting factor by transforming growth factor-beta
Feifei CHEN;
Feifei CHEN
Department of Medical Molecular Genetics the Walther Oncology Center, Indiana University School of Medicine, the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A.
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Kenji OGAWA;
Kenji OGAWA
Department of Medical Molecular Genetics the Walther Oncology Center, Indiana University School of Medicine, the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A.
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Raman P. NAGARAJAN;
Raman P. NAGARAJAN
Department of Medical Molecular Genetics the Walther Oncology Center, Indiana University School of Medicine, the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A.
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Meiyu ZHANG;
Meiyu ZHANG
Department of Medical Molecular Genetics the Walther Oncology Center, Indiana University School of Medicine, the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A.
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Chenzhong KUANG;
Chenzhong KUANG
Department of Medical Molecular Genetics the Walther Oncology Center, Indiana University School of Medicine, the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A.
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Yan CHEN
Yan CHEN
1
Department of Medical Molecular Genetics the Walther Oncology Center, Indiana University School of Medicine, the Walther Cancer Institute, Indianapolis, IN 46202, U.S.A.
1To whom correspondence should be sent, at the following address: Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut Street, IB130, Indianapolis, IN 46202, U.S.A. (e-mail ychen3@iupui.edu).
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Publisher: Portland Press Ltd
Received:
January 09 2003
Revision Received:
February 11 2003
Accepted:
February 20 2003
Accepted Manuscript online:
February 20 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (2): 257–263.
Article history
Received:
January 09 2003
Revision Received:
February 11 2003
Accepted:
February 20 2003
Accepted Manuscript online:
February 20 2003
Citation
Feifei CHEN, Kenji OGAWA, Raman P. NAGARAJAN, Meiyu ZHANG, Chenzhong KUANG, Yan CHEN; Regulation of TG-interacting factor by transforming growth factor-beta. Biochem J 15 April 2003; 371 (2): 257–263. doi: https://doi.org/10.1042/bj20030095
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