Transcription of the transforming growth factor-beta 2 gene is dependent on an E-box located between an essential cAMP response element/activating transcription factor motif and the TATA box of the gene

被引:41
作者
Scholtz, B
KingsleyKallesen, M
Rizzino, A
机构
[1] UNIV NEBRASKA, MED CTR, EPPLEY INST RES CANC & ALLIED DIS, OMAHA, NE 68198 USA
[2] UNIV NEBRASKA, MED CTR, DEPT PATHOL & MICROBIOL, OMAHA, NE 68198 USA
关键词
D O I
10.1074/jbc.271.50.32375
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transforming growth factor-beta 2 (TGF-beta 2) is an important regulator of cell proliferation and differentiation; however, its transcriptional regulation is not well understood, Here we report characterization of an essential E-box motif, positioned at -50/-45 between a previously described functional cAMP response element/activating transcription factor site and the TATA box of the human TGF-beta 2 promoter, By site directed mutagenesis, we demonstrate that this E-box motif is necessary for the promoter activity, not only in differentiated cells derived from embryonal carcinoma cells, but also in choriocarcinoma cells and in MCF-7 breast carcinoma cells, We also demonstrate that the transcription factors USF1 and USF2 bind to this E-box motif in vitro when nuclear extracts from each of these cell lines are examined by gel retardation assays, Moreover, using a dominant-negative USF2 protein, we show that USF proteins are critical for TGF-beta 2 promoter activity in vivo. The importance of the E-box motif described in this study is supported by the presence of an E-box motif in the same position in the chicken TGF-beta 2 gene promoter.
引用
收藏
页码:32375 / 32380
页数:6
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