Plakoglobin as a regulator of desmocollin gene expression.
Plakoglobin as a regulator of desmocollin gene expression.
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DOI：
10.1038/jid.2013.220
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发表时间：
2013-12
影响因子：
6.5
通讯作者：
Koch, Peter J.
中科院分区：
文献类型：
--
作者：
Tokonzaba, Etienne;Chen, Jiangli;Cheng, Xing;Den, Zhining;Ganeshan, Radhika;Muller, Eliane J.;Koch, Peter J.
桥粒是哺乳动物组织和器官(如皮肤、皮肤附属物和心脏)正常发育和维持所需的细胞黏附连接。本研究的目的是研究桥粒的跨膜成分桥粒(DSC)是如何在转录水平上被调控的。我们假设Dsc2和Dsc3基因的差异表达是皮肤附属物正常发育的先决条件。我们证明，Pg和Lef-1一起对这两个基因的近端启动子起着不同的调节作用。具体地说，我们发现Lef-1在PG存在的情况下发挥着激活Dsc2和抑制Dsc3的开关作用。有趣的是，我们还确定了作为EDA/κ信号级联下游效应器的NFDSC2 B通路组件可以激活Dsc2的表达。我们推测在胎盘角质形成细胞中，LeF-1和EDA/EDAR/NFDSCB信号参与了κ异构体表达从Dsc3到Dsc2的转变。人们很容易推测，这种转变是胎盘角质形成细胞进入真皮的侵袭性生长所必需的，这是皮肤附件形成的关键步骤。
Desmosomes are cell adhesion junctions required for the normal development and maintenance of mammalian tissues and organs such as the skin, skin appendages and the heart. The goal of the present study was to investigate how desmocollins (DSC), transmembrane components of desmosomes, are regulated at the transcriptional level. We hypothesized that differential expression of the Dsc2 and Dsc3 genes is a prerequisite for normal development of skin appendages. We demonstrate that plakoglobin (Pg) in conjunction with Lef-1 differentially regulates the proximal promoters of these two genes. Specifically, we found that Lef-1 acts as a switch activating Dsc2 and repressing Dsc3 in the presence of Pg. Interestingly, we also determined that NFκB pathway components, down-stream effectors of the Eda/EDAR signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and Eda/EDAR/NFκB signaling contribute to a shift in Dsc isoform expression from Dsc3 to Dsc2 in placode keratinocytes. It is tempting to speculate that this shift is required for invasive growth of placode keratinocytes into the dermis, a crucial step in skin appendage formation.
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影响因子：
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