Wasylyk C, Gutman A, Nicholson R, Wasylyk B
CNRS-LGME/INSERM U184, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
EMBO J. 1991 May;10(5):1127-34. doi: 10.1002/j.1460-2075.1991.tb08053.x.
The c-ets protooncogenes have recently been shown to code for transcription factors that activate the oncogene responsive unit of the polyoma virus enhancer. We show that transcription of the stromelysin gene, which is highly expressed in transformed cells and tumours, is efficiently activated by c-Ets-1 and -2 through two DNA elements. The distal element is a highly conserved palindrome composed of two strong binding sites for c-Ets-1. The proximal element does not bind c-Ets-1, but may be activated indirectly by increased synthesis of c-Jun and c-Fos. Both ets responsive elements mediate activation by the oncoproteins Ha-Ras, v-Src and v-Mos. These results suggest that c-Ets participates in the mechanisms by which stromelysin gene expression is deregulated in transformed cells and tumours.
最近研究表明,c-ets原癌基因编码的转录因子可激活多瘤病毒增强子的癌基因反应单元。我们发现,在转化细胞和肿瘤中高表达的基质金属蛋白酶基因的转录,可被c-Ets-1和c-Ets-2通过两个DNA元件有效激活。远端元件是一个高度保守的回文结构,由两个c-Ets-1的强结合位点组成。近端元件不结合c-Ets-1,但可能通过c-Jun和c-Fos合成增加而间接激活。这两个ets反应元件均可介导癌蛋白Ha-Ras、v-Src和v-Mos的激活作用。这些结果表明,c-Ets参与了转化细胞和肿瘤中基质金属蛋白酶基因表达失调的机制。