Retinoic acid inhibits transformation by preventing phosphatidylinositol 3-kinase dependent activation of the c-fos promoter.
Retinoic acid inhibits transformation by preventing phosphatidylinositol 3-kinase dependent activation of the c-fos promoter.
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视黄酸通过阻止 c-fos 启动子的磷脂酰肌醇 3 激酶依赖性激活来抑制转化。
DOI：
10.1038/sj.onc.1202272
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发表时间：
1999
期刊：
影响因子：
8
通讯作者：
Talmage,DA
中科院分区：
文献类型：
--
作者：
Chen,Y;Freund,R;Listerud,M;Wang,Z;Talmage,DA
视黄酸抑制多瘤病毒中间T癌蛋白对细胞的转化。转化的抑制是由于视黄酸依赖的细胞不能完全表达c-fos原癌基因。维甲酸通过破坏质膜上酪氨酸激酶和c-fos启动子上反式作用因子之间的信号传导来阻止c-fos启动子的反式活化。我们采用互补的遗传、生化和分子方法证明：(1)磷脂酰肌醇3激酶信号是多瘤病毒中间T癌蛋白激活c-fos表达的主要机制；(2)中间T/磷脂酰肌醇3-激酶c-fos启动子的转激活和细胞的转化需要激活小gtp结合蛋白Rac和Jun n -末端激酶；(3)维甲酸抑制Jun n -末端激酶的活化，从而阻止c-fos的反活化和转化；(4) c-fos转录的中间T激活需要血清反应元件和启动子近端环AMP反应元件。这些研究确定了一个新的靶点，通过它类维生素a可以预防致癌转化。
Retinoic acid inhibits transformation of cells by polyoma virus middle T oncoprotein. Inhibition of transformation results from a retinoic acid-dependent failure of cells to fully express the c-fos proto-oncogene. Retinoic acid prevents transactivation of the c-fos promoter by disrupting signaling between tyrosine kinases at the plasma membrane and trans-acting factors at the c-fos promoter. We used complementary genetic, biochemical and molecular approaches to demonstrate that:(1) phosphatidylinositol 3-kinase signaling is the principle mechanism of polyoma virus middle T oncoprotein activation of c-fos expression;(2) middle T/phosphatidylinositol 3-kinase transactivation of the c-fos promoter and transformation of cells requires activation of both the small GTP-binding protein Rac and Jun N-terminal kinase;(3) retinoic acid inhibits activation of Jun N-terminal kinase, thereby preventing c-fos transactivation and transformation; and (4) middle T activation of c-fos transcription requires both the serum response element and the promoter proximal cyclic AMP response element. These studies identify a novel target through which retinoids prevent oncogenic transformation.