Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation.
Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation.
复制标题
DOI：
10.1101/gad.6.9.1799
复制
发表时间：
1992-09
影响因子：
10.5
通讯作者：
S. Oliviero;G. Robinson;K. Struhl;Bruce M. Spiege
中科院分区：
文献类型：
--
作者：
S. Oliviero;G. Robinson;K. Struhl;Bruce M. Spiege
Jun 和 Fos 癌蛋白属于转录激活因子 AP-1 家族，被认为通过不适当地激活参与细胞复制的基因来诱导细胞转化。为了确定通过 AP-1 位点的转录激活是否足以实现转化活性，我们检查了大鼠胚胎成纤维细胞中自主异源 AP-1 蛋白（酵母 GCN4）的特性。 GCN4 通过 AP-1 位点诱导转录激活，但与 Jun 和 Fos 不同，它无法与 Ha-ras 合作诱导细胞转化。 Jun-GCN4 和 Fos-GCN4 同二聚体独立诱导细胞转化，表明 Jun 和 Fos 的氨基末端区域各自包含肿瘤发生所需的调节功能，但与通用转录激活结构域不同。此外，这些观察结果对响应 Jun 和 Fos 的致癌相关靶基因的性质也有影响。
The Jun and Fos oncoproteins belong to the AP-1 family of transcriptional activators and are believed to induce cellular transformation by inappropriately activating genes involved in cell replication. To determine whether transcriptional activation through AP-1 sites is sufficient for transforming activity, we examined the properties of an autonomous and heterologous AP-1 protein, yeast GCN4, in rat embryo fibroblasts. GCN4 induces transcriptional activation through AP-1 sites but, unlike Jun and Fos, fails to induce cellular transformation, in cooperation with Ha-ras. Jun-GCN4 and Fos-GCN4 homodimers independently induce cellular transformation indicating that the amino-terminal regions of Jun and Fos each contain regulatory functions that are required for oncogenesis but are distinct from generic transcriptional activation domains. In addition, these observations have implications for the nature of the oncogenically relevant target genes that respond to Jun and Fos.