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人角质形成细胞转谷氨酰胺酶启动子中功能性AP1和CRE反应元件介导Whn抑制。

Functional AP1 and CRE response elements in the human keratinocyte transglutaminase promoter mediating Whn suppression.

作者信息

Jessen B A, Qin Q, Rice R H

机构信息

Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616-8588, USA.

出版信息

Gene. 2000 Aug 22;254(1-2):77-85. doi: 10.1016/s0378-1119(00)00291-2.

DOI:10.1016/s0378-1119(00)00291-2
PMID:10974538
Abstract

Expression of keratinocyte transglutaminase (TGM1) is critical for maturation of mammalian epidermis and occurs during squamous metaplasia. Examination of the TGM1 5'-flanking region in transient transfections of human epidermal cells revealed an AP1 site approximately 1.5kb upstream from the transcription start site and a CRE site approximately 0.5kb upstream that, combined, accounted for as much as 90% of the transcriptional activity. Upon incubation with nuclear extract, three electrophoretically separable protein complexes were formed by a CRE site oligonucleotide, one of which was competed by an AP1 response element. In super-shift analysis, c-Jun and JunD formed complexes with both the AP1 and CRE sequences. The AP1 and CRE sites were found to mediate the suppressive effects of the Whn transcription factor on the activity of the TGM1 promoter. Similarly, two previously described AP1 sites mediated Whn suppression of involucrin promoter activity.

摘要

角质形成细胞转谷氨酰胺酶(TGM1)的表达对于哺乳动物表皮的成熟至关重要,且发生于鳞状化生过程中。对人表皮细胞瞬时转染中的TGM1 5'-侧翼区域进行检测发现,在转录起始位点上游约1.5kb处有一个AP1位点,在其上游约0.5kb处有一个CRE位点,二者共同构成了高达90%的转录活性。与核提取物孵育后,一个CRE位点寡核苷酸形成了三种可通过电泳分离的蛋白质复合物,其中一种可被AP1反应元件竞争。在超迁移分析中,c-Jun和JunD与AP1和CRE序列均形成复合物。发现AP1和CRE位点介导了Whn转录因子对TGM1启动子活性的抑制作用。同样,两个先前描述的AP1位点介导了Whn对兜甲蛋白启动子活性的抑制作用。

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