Rossi A, Jang S I, Ceci R, Steinert P M, Markova N G
Department of Experimental Medicine, University of Tor Vergata, Rome, Italy.
J Invest Dermatol. 1998 Jan;110(1):34-40. doi: 10.1046/j.1523-1747.1998.00071.x.
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 AP1 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.
基底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表皮蛋白以分化特异性模式的合成。这些表皮标记基因中的几个在其启动子区域通过激活蛋白1（AP1）相互作用来调节转录。在表皮中，各种AP1转录因子并非均匀分布，而是似乎具有分化特异性分布。我们探究了AP1对角蛋白5、转谷氨酰胺酶1、内披蛋白和兜甲蛋白基因的调控表达是否反映了AP1因子在表皮中的分布。我们发现c-jun和junD激活，而junB下调基底和基底上层基因的转录。c-jun的作用是通过与靶启动子中AP1基序处的c-fos相互作用来实现的，而junB和junD的作用独立于在AP1位点的结合。因此，c-jun和junD作为一般的正调控因子，而junB作为表皮特异性基因的一般抑制因子。所以，AP1调控的分化特异性不仅必须由不同的DNA/AP1复合物的形成来决定，还必须由涉及其他转录调节因子和/或远端调节元件的相互作用来决定。
