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- W2045179462 abstract "We have previously demonstrated enhanced transcriptional activity of the human Pi class glutathione <i>S</i>-transferase (<i>GSTP1</i>) promoter in a multidrug-resistant derivative (VCREMS) of the human mammary carcinoma cell line, MCF7 (Moffat, G. J., McLaren, A. W., and Wolf, C. R. (1994) <i>J. Biol. Chem.</i> 269, 16397-16402). Furthermore, we have identified an essential sequence (C1; −70 to −59) within the <i>GSTP1</i> promoter that bound a Jun-Fos heterodimer in VCREMS but not in MCF7 cells. These present studies have examined the negative regulatory element (−105 to −86), which acted to suppress <i>GSTP1</i> transcription in MCF7 cells. Mutational analysis of this silencer element further defined the repressor binding site to be located between nucleotides −97 and −90. <i>In vitro</i> DNA binding assays suggested that the repressor exerted its action by causing displacement of the essential non-AP-1-like MCF7 C1 complex. However, the addition of MCF7 nuclear extract did not disrupt binding of the VCREMS Jun-Fos C1 complex to the <i>GSTP1</i> promoter. Furthermore, upstream insertion of the <i>GSTP1</i> silencer element failed to inhibit activity of a heterologous promoter in MCF7 cells. These results highlighted the cell and promoter specificity of the <i>GSTP1</i> transcriptional repressor and implicated a functional requirement for contact between the repressor and C1 complex. In this regard, the introduction of half-helical turns between the silencer and the C1 element abrogated repressor activity, thus leading to the hypothesis that a direct interaction between the repressor and C1 complex was required to suppress <i>GSTP1</i> transcription. Moreover, these findings suggest that cell-specific differences in the composition of the C1 nuclear complex may dictate repressor activity." @default.
- W2045179462 created "2016-06-24" @default.
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- W2045179462 date "1996-08-01" @default.
- W2045179462 modified "2023-10-17" @default.
- W2045179462 title "Functional Characterization of the Transcription Silencer Element Located within the Human Pi Class Glutathione S-Transferase Promoter" @default.
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- W2045179462 doi "https://doi.org/10.1074/jbc.271.34.20740" @default.
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