The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression

The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression
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DOI:
10.1093/emboj/19.9.2024
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发表时间:
2000-05-02
期刊:
影响因子:
11.4
通讯作者:
Matter, K
Matter, K
中科院分区:
生物学1区
文献类型:
--
作者:
Balda, MS;Matter, K

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上皮紧密连接调节细胞旁扩散,并限制顶端和基底外侧质膜成分的混合。我们现在鉴定出一种Y - box转录因子,即ZONAB(紧密连接蛋白1相关核酸结合蛋白),它与紧密连接的膜下蛋白ZO - 1的SH3结构域结合。ZONAB定位于细胞核和紧密连接处,并与含有反向CCAAT盒的特定启动子序列结合。在报告基因检测中,ZONAB和ZO - 1以细胞密度依赖的方式在ErbB - 2启动子的调控中发生功能性相互作用。在稳定转染过表达的细胞中,ZO - 1和ZONAB控制内源性ErbB - 2的表达,并在细胞旁通透性的调控中起作用。这些数据表明紧密连接直接参与基因表达的控制,并提示它们在上皮细胞分化的调控中起作用。
Epithelial tight junctions regulate paracellular diffusion and restrict the intermixing of apical and basolateral plasma membrane components. We now identify a Y-bos transcription factor, ZONAB (-1-associated nucleic acid-binding protein), that binds to the SH3 domain of ZO-1, a submembrane protein of tight junctions. ZONAB localizes to the nucleus and at tight junctions, and binds to sequences of specific promoters containing an inverted CCAAT hox. In reporter assays, ZONAB and ZO-1 functionally interact in the regulation of the ErbB-2 promoter in a cell density-dependent manner. In stably transfected over-expressing cells, ZO-1 and ZONAB control expression of endogenous ErbB-2 and function in the regulation of paracellular permeability. These data indicate that tight junctions directly participate in the control of gene expression and suggest that they function in the regulation of epithelial cell differentiation.