Oridate N, Nishi S, Inuyama Y, Sakai M
Department of Biochemistry, Hokkaido University School of Medicine, Sapporo, Japan.
Biochim Biophys Acta. 1994 Oct 18;1219(2):499-504. doi: 10.1016/0167-4781(94)90077-9.
The rat glutathione transferase P gene has a strong enhancer element, termed GPE I, which is composed of a dyad of palindromicly oriented TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive element (TRE)-like sequences. TRE is a binding sequence of the transcription factor AP-1, which consists of several closely related proteins belonging to the Jun and Fos family. The gel retardation experiments show that all the heterodimers formed between the Jun and Fos related gene products bind to the GPE I as well as to the TRE. In spite of the fact that the GPE I has a stronger activity than the TRE, the binding affinities of these heterodimers to the GPE I are much lower than to the TRE. Co-transfection studies of the reporter construct containing the GPE I and expression constructs of each of the Jun and Fos family cDNAs indicate that FosB and delta FosB repress transcription through the GPE I enhancer. These results suggests that some of Jun/Fos family may regulate the rat GST-P gene expression through the GPE I in vivo.
大鼠谷胱甘肽转移酶P基因有一个强增强子元件,称为GPE I,它由一对呈回文方向排列的佛波醇12 - O -十四烷酸酯13 - 乙酸酯(TPA)反应元件(TRE)样序列组成。TRE是转录因子AP - 1的结合序列,AP - 1由几个属于Jun和Fos家族的密切相关蛋白组成。凝胶阻滞实验表明,Jun和Fos相关基因产物之间形成的所有异二聚体都能与GPE I以及TRE结合。尽管GPE I的活性比TRE强,但这些异二聚体与GPE I的结合亲和力远低于与TRE的结合亲和力。对含有GPE I的报告基因构建体与Jun和Fos家族每个cDNA的表达构建体进行共转染研究表明,FosB和δFosB通过GPE I增强子抑制转录。这些结果表明,Jun/Fos家族的一些成员可能在体内通过GPE I调节大鼠GST - P基因的表达。