c-Jun-mediated repression and transactivation of fibronectin.
c-Jun-mediated repression and transactivation of fibronectin.
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DOI：
10.3892/mmr.1.1.99
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发表时间：
2008
影响因子：
3.4
通讯作者：
Yukio Hayashi;Y. Shino;Kengo Saito;H. Tanzawa;H. Shirasawa
中科院分区：
文献类型：
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作者：
Yukio Hayashi;Y. Shino;Kengo Saito;H. Tanzawa;H. Shirasawa
纤连蛋白 (FN) 被人乳头瘤病毒 16 型 (HPV16) E6 通过诱导 c-Jun-ATF-2 复合物与 FN 启动子中的环 AMP 反应元件 (CRE) 结合而反式激活。本研究分析了 c-Jun 对 FN 基因表达的调节。 Northern 和免疫印迹分析表明，c-Jun 表达在 HPV16-E6 表达细胞中增强。然而，过表达c-Jun的小鼠10T1/2细胞系显示c-Jun的表达水平与FN的表达水平之间呈负相关。荧光素酶测定表明，FN 启动子在 c-Jun 过表达的小鼠 10T1/2 细胞中受到强烈抑制。 FN启动子的缺失和突变分析表明，c-Jun对FN启动子的抑制取决于位于相对于转录起始位点-160的CRE。对来自 HPV16-E6 表达和 c-Jun 过表达细胞的 CRE 结合复合物进行 Supershift 测定表明，与 CRE 结合的复合物中存在 ATF-2，这是 FN 基因反式激活所必需的。总的来说，我们的研究表明，根据细胞环境，FN 基因可以被 c-Jun 反式激活或抑制。
Fibronectin (FN) is transactivated by human papillomavirus type 16 (HPV16) E6 via the induction of c-Jun-ATF-2 complexes binding to the cyclic AMP response element (CRE) in the FN promoter. The present study analyzed c-Jun regulation of FN gene expression. Northern and immunoblot analyses showed that c-Jun expression was enhanced in HPV16-E6-expressing cells. However, mouse 10T1/2 cell lines overexpressing c-Jun showed an inverse correlation between the expression levels of c-Jun and those of FN. Luciferase assays indicated that the FN promoter was strongly repressed in c-Jun-overexpressing mouse 10T1/2 cells. Deletion and mutation analyses of the FN promoter revealed that repression of the FN promoter by c-Jun depends on the CRE located at -160 relative to the start site of transcription. Supershift assays of CRE-bound complexes from HPV16-E6-expressing and c-Jun-overexpressing cells suggested that the presence of ATF-2 in the complexes binding to CRE was required for the transactivation of the FN gene. Collectively, our study suggests that the FN gene can be either transactivated or repressed by c-Jun depending on the cell context.