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J Biol Chem, Vol. 273, Issue 40, 25929-25936, October 2, 1998
From the 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)-
Molecular Cloning and Characterization of TIEG2
Reveals a New Subfamily of Transforming Growth Factor-
-inducible
Sp1-like Zinc Finger-encoding Genes Involved in the Regulation of Cell
Growth
,,, and¶
Gastroenterology Research Unit, Department of Biochemistry and Molecular Biology,
-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--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-sulfophenyl)-2H-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--inducible Sp1-like
proteins involved in the regulation of cell growth.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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