Plakoglobin regulates the expression of the anti-apoptotic protein BCL-2
Plakoglobin regulates the expression of the anti-apoptotic protein BCL-2
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DOI：
10.1074/jbc.275.15.10905
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发表时间：
2000-04-14
影响因子：
4.8
通讯作者：
Pasdar, M
中科院分区：
文献类型：
--
作者：
Hakimelahi, S;Parker, HR;Pasdar, M
斑珠蛋白是一种细胞质蛋白，是β-连环蛋白和果蝇Armadillo蛋白的同源物，具有相似的粘附和信号传导功能。斑珠蛋白与钙粘蛋白相互作用，介导细胞间粘附，并与转录因子结合，诱导参与细胞命运决定和增殖的基因表达变化。与β-连环蛋白通过激活c-MYC和细胞周期蛋白D1基因表达在细胞增殖中的相对较好表征的作用不同，斑珠蛋白在调节细胞生长中的信号传导功能尚未确定。在这里，我们表明，斑珠蛋白缺乏的人SCC 9细胞中斑珠蛋白的高水平表达导致不受控制的生长和病灶形成。与生长特征的变化同时，我们观察到细胞凋亡的明显抑制，这与BCL-2的表达诱导相关，BCL-2是细胞凋亡调节蛋白的原型成员。BCL-2的表达与减少的蛋白水解加工和caspase-3的激活相一致，caspase-3是程序性细胞死亡的执行者。我们的数据表明，斑珠蛋白的生长调节功能是独立的，它在介导细胞-细胞粘附的作用，这些观察清楚地牵连斑珠蛋白在调节细胞生长的途径，并提供了初步的证据，它的作用作为一个关键的分子之间的联系调节细胞粘附和细胞死亡的途径。
Plakoglobin is a cytoplasmic protein and a homologue of beta-catenin and Armadillo of Drosophila with similar adhesive and signaling functions, These proteins interact with cadherins to mediate cell-cell adhesion and associate with transcription factors to induce changes in the expression of genes involved in cell fate determination and proliferation. Unlike the relatively well characterized role of beta-catenin in cell proliferation via activation of c-MYC and cyclin D1 gene expression, the signaling function of plakoglobin in regulation of cell growth is undefined. Here, we show that high levels of plakoglobin expression in plakoglobin-deficient human SCC9 cells leads to uncontrolled growth and foci formation. Concurrent with the change in growth characteristics we observe a pronounced inhibition of apoptosis, This correlates with an induction of expression of BCL-2, a prototypic member of apoptosis-regulating proteins. The BCL-2 expression coincides with decreased proteolytic processing and activation of caspase-3, an executor of programmed cell death. Our data suggest that the growth regulatory function of plakoglobin is independent of its role in mediating cell-cell adhesion, These observations clearly implicate plakoglobin in pathways regulating cell growth and provide initial evidence of its role as a pivotal molecular link between pathways regulating cell adherence and cell death.