Transcriptional activation of a conserved sequence element by ras requires a nuclear factor distinct from c-fos or c-jun.
Transcriptional activation of a conserved sequence element by ras requires a nuclear factor distinct from c-fos or c-jun.
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ras 对保守序列元件的转录激活需要不同于 c-fos 或 c-jun 的核因子。
DOI：
10.1073/pnas.87.10.3866
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发表时间：
1990
影响因子：
11.1
通讯作者：
Ostrowski,MC
中科院分区：
文献类型：
--
作者：
Owen,RD;Ostrowski,MC
Ras条件性表达可增加转化生长因子β1mRNA的表达。在编码人转化生长因子β1的基因上游发现了一个约420个碱基对的序列，作为ras反应的增强子元件在瞬时转染试验中发挥作用。人的序列包含TGACTCT元件，该元件也存在于小鼠RAS反应增强子中。对ras稳定转化的细胞中存在的核因子的分析表明，人类和小鼠的序列都被相同的核因子识别。在使用含有TGACTCT或TGAGTAA的小鼠元件的转染实验中，分析了Fos和Jun在ras转录激活中的作用。这些实验表明，虽然这两个元件都被Fos/Jun表达激活到几乎相同的事件，但只有前一个元件对ras做出反应。此外，RAS对含有TGACTCT的记者的激活是FOS/JUN的6倍。凝胶保留实验表明，ras转化的细胞中存在的核因子表现出与瞬时转染实验中相同的序列偏好。紫外光交联实验确定了一种表观分子质量为120 kDa的蛋白质，它识别ras反应元件。这项工作发现了一条持久的信号转导途径，将ras与核转录联系起来，并表明120 kDa的蛋白是这一途径的靶标。
The expression of transforming growth factor beta type 1 mRNA was increased by conditional expression of ras. A 31-base-pair sequence found approximately 420 base pairs upstream of the gene encoding human transforming growth factor beta 1 acted as a ras-responsive enhancer element in transient transfection assays. The human sequence contains the element TGACTCT that also is found in a murine ras-responsive enhancer. Analysis of nuclear factors present in cells stably transformed by ras indicated that both human and murine sequences were recognized by the same nuclear factor. The role of fos and jun in ras transcriptional activation was analyzed in transfection assays using murine elements that contained either TGACTCT or TGAGTAA. These experiments showed that while both elements are activated by fos/jun expression to nearly the same event, only the former element responded to ras. In addition, activation of reporters containing TGACTCT is 6-fold higher by ras than by fos/jun. Gel retention experiments revealed that the nuclear factor present in cells transformed by ras exhibited the same sequence preference as demonstrated in the transient transfection assays. UV-crosslinking experiments identify a protein of apparent molecular mass 120 kDa that recognizes the ras-responsive element. This work identifies a persistent signal transduction pathway that links ras to nuclear transcription and indicates that a 120-kDa protein is a target of this pathway.