Effect of AP1 transcription factors on the regulation of transcription in normal human epidermal keratinocytes
Effect of AP1 transcription factors on the regulation of transcription in normal human epidermal keratinocytes
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DOI：
10.1046/j.1523-1747.1998.00071.x
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发表时间：
1998-01-01
影响因子：
6.5
通讯作者：
Markova, NG
中科院分区：
文献类型：
--
作者：
Rossi, A;Jang, SI;Markova, NG
基底层角质形成细胞向棘状细胞和颗粒细胞的转化伴随着一系列具有分化特异性的表皮蛋白的合成。其中几个表皮标记基因的转录受其启动子区域的激活蛋白1(AP1)相互作用的调节。在表皮中，不同的AP1转录因子并不是统一存在的，但似乎具有分化特异性的分布。我们已经探索了AP1调控的角蛋白5、转谷氨酰胺酶1、总蛋白和氯化蛋白基因的表达是否反映了AP1因子在表皮中的分布。我们发现c-jun和Jund激活，JunB下调基础和超基础基因的转录。C-jun的作用是通过与靶启动子中AP1基序上的c-fos相互作用来实现的，而JunB和Jund的作用都不依赖于AP1位点的结合。因此，c-Jun和Jund作为一般的正调控因子，而JunB则作为表皮特异性基因的一般抑制因子。因此，API调控的分化特异性不仅取决于不同DNA/AP1复合体的形成，还取决于其他转录调控因子和/或远端调控元件的相互作用。
The conversion of basal keratinocytes to spinous and granular cells is accompanied by the synthesis of a series of epidermal proteins in a differentiation-specific pattern. The transcription of several of these epidermal marker genes is regulated by activator protein 1 (AP1) interactions at their promoter regions. In the epidermis the various AP1 transcription factors are not present uniformly but appear to have a differentiation-specific distribution. We have explored whether the AP1 regulated expression of the keratin 5, transglutaminase 1, involucrin, and loricrin genes reflects the distribution of the AP1 factors in the epidermis. We have found that c-jun and junD activate and junB downregulates the transcription of both basal and suprabasal genes. The effect of c-jun is exerted through interactions with c-fos at the AP1 motifs in the target promoters, whereas both junB and junD act independently of the binding at the AP1 sites. Thus c-jun and junD act as general positive regulators whereas junB acts as a general suppressor of epidermal-specific genes. Therefore, the differentiation specificity of the API regulation must be determined not only by the formation of distinct DNA/AP1 complexes but also by interactions involving other transcriptional regulators and/or distal regulatory elements.