Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth
Autor: | Raul Urrutia, Ann Mladek, Tiffany Cook, Brian Gebelein, Kristin Mesa |
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Rok vydání: | 1998 |
Předmět: |
Sp1 Transcription Factor
Molecular Sequence Data Kruppel-Like Transcription Factors Apoptosis Cell Cycle Proteins CHO Cells Biology Biochemistry Transforming Growth Factor beta Cricetinae Animals Humans Amino Acid Sequence RNA Messenger Nuclear protein Cloning Molecular Molecular Biology Gene Transcription factor Zinc finger Sequence Homology Amino Acid Cell growth Chinese hamster ovary cell Nuclear Proteins Zinc Fingers Cell Biology Sequence Analysis DNA Molecular biology DNA-Binding Proteins Repressor Proteins Gene Expression Regulation Microscopy Fluorescence Transforming growth factor beta 3 Early Growth Response Transcription Factors Apoptosis Regulatory Proteins Cell Division Transforming growth factor Transcription Factors |
Zdroj: | The Journal of biological chemistry. 273(40) |
ISSN: | 0021-9258 |
Popis: | Sp1-like zinc finger transcription factors are involved in the regulation of cell growth and differentiation. Recent evidence demonstrating that mammalian cells express novel, yet uncharacterized, Sp1-like proteins has stimulated a search for new members of this family. We and others have recently reported that the transforming growth factor (TGF)-beta-regulated gene TIEG encodes a new Sp1-like protein that inhibits cell growth in cultured cells. Here we report the identification, nuclear localization, DNA binding activity, transcriptional repression activity, and growth inhibitory effects of TIEG2, a novel TGF-beta-inducible gene related to TIEG. TIEG2 is ubiquitously expressed in human tissues, with an enrichment in pancreas and muscle. TIEG2 shares 91% homology with TIEG1 within the zinc finger region and 44% homology within the N terminus. Biochemical characterization reveals that TIEG2 is a nuclear protein, which, as predicted from the primary structure, specifically binds to an Sp1-like DNA sequence in vitro and can repress a promoter containing Sp1-like binding sites in transfected Chinese hamster ovary epithelial cells. Furthermore, functional studies using [3H]thymidine uptake and MTS (3-(4, 3-dimethyltiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-su lfophenyl)-2 H-tetrazolium) assays demonstrate that the overexpression of TIEG2 in Chinese hamster ovary cells inhibits cell proliferation. Thus, TIEG2, together with TIEG1, defines a new subfamily of TGF-beta-inducible Sp1-like proteins involved in the regulation of cell growth. |
Databáze: | OpenAIRE |
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