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Volume 272, Number 22,
Issue of May 30, 1997
pp. 14244-14250
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Transcription Factor AP-2 Controls Transcription of the Human
Transforming Growth Factor- Gene
(Received for publication, May 13, 1996, and in revised form, February 18, 1997)
Dongyan
Wang
,
Tae Ho
Shin
and
Jeffrey E.
Kudlow
From the Departments of Medicine and Cell Biology, Division of
Endocrinology and Metabolism, The University of Alabama at
Birmingham, Birmingham, Alabama 35294
The epidermal growth factor receptor is vital for
normal development and plays a role in oncogenesis. The level of
activation of this receptor by transforming growth factor- (TGF- )
is controlled, in part, by the rate of transcription of the TGF-
gene. In the characterization of the proximal TGF- promoter by DNase
I footprinting, a 43-base pair element ( 88 to 130 relative to the
transcription start site), designated T RE I, was found that was
specifically protected by nuclear proteins from human mammary carcinoma
MDA468 cells. T RE I was essential for the maximal expression of the TGF- gene as indicated by deletion and mutagenesis analyses. T RE
I consists of two cis-acting elements, a proximal
regulatory element (PRE, 89 to 103) and a distal regulatory element
(DRE, 121 to 128). Both elements were able to form specific
complexes with protein from MDA468 cell nuclear extracts and are
necessary for the full activity of the entire 1.1-kilobase pair TGF-
promoter. Competition and antibody studies determined that the DRE
contains a binding site for the transcription factor AP-2, while the
protein that binds to the PRE has yet to be identified. When linked
upstream to the heterologous herpes simplex thymidine kinase promoter, the T RE I enhanced transcription up to 11-fold in MDA468 cells. Cotransfection of an AP-2 expression vector was able to activate transcription from the T REI-TK construct in a
DRE-dependent manner. These results further our
understanding of how TGF- transcription is regulated.

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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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