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. J Biol Chem 1998 Oct 02;273(40):25929-36
Date
09/25/1998Pubmed ID
9748269DOI
10.1074/jbc.273.40.25929Scopus ID
2-s2.0-0032475869 (requires institutional sign-in at Scopus site) 171 CitationsAbstract
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.
Author List
Cook T, Gebelein B, Mesa K, Mladek A, Urrutia RAuthor
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Apoptosis
Apoptosis Regulatory Proteins
CHO Cells
Cell Cycle Proteins
Cell Division
Cloning, Molecular
Cricetinae
DNA-Binding Proteins
Early Growth Response Transcription Factors
Gene Expression Regulation
Humans
Kruppel-Like Transcription Factors
Microscopy, Fluorescence
Molecular Sequence Data
Nuclear Proteins
RNA, Messenger
Repressor Proteins
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Sp1 Transcription Factor
Transcription Factors
Transforming Growth Factor beta
Zinc Fingers