Plakoglobin deficiency protects keratinocytes from apoptosis
Plakoglobin deficiency protects keratinocytes from apoptosis
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DOI：
10.1038/sj.jid.5700615
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发表时间：
2007-04-01
影响因子：
6.5
通讯作者：
Green, Kathleen J.
中科院分区：
文献类型：
--
作者：
Dusek, Rachel L.;Godsel, Lisa M.;Green, Kathleen J.
犰狳家族蛋白斑珠蛋白（Pg）是锚定连接的充分表征的组分，在锚定连接处，其功能是介导细胞-细胞粘附并维持上皮组织完整性。尽管其最接近的同源物β-连环蛋白在Writ信号通路中起作用以决定细胞命运并促进增殖和存活，但Pg在这些过程中的作用还不清楚。在这里，我们调查如何Pg影响小鼠角质形成细胞的生存，通过挑战两个Pg-空细胞和它们的杂合子对应凋亡刺激。我们的研究结果表明，Pg缺失保护角质形成细胞免于凋亡，空细胞表现出延迟的线粒体细胞色素c释放和caspase-3的激活。与杂合子对照相比，PG缺失的角质形成细胞还表现出抗凋亡分子Bcl-X-L的信使RNA和蛋白质水平增加。重要的是，将Pg重新引入到空细胞中使其表型向Pg+/-角质形成细胞的表型转变，提供了Pg在调节细胞存活中起直接作用的进一步证据。两者合计，我们的研究结果表明，除了其在上皮细胞中的粘附作用，Pg也可以在相反的β-连环蛋白的prosurvival倾向，以加强细胞凋亡刺激损伤的细胞死亡，也许限制了潜在的突变和细胞转化的传播。
The armadillo family protein plakoglobin (Pg) is a well-characterized component of anchoring junctions, where it functions to mediate cell-cell adhesion and maintain epithelial tissue integrity. Although its closest homolog, ss-catenin acts in the Writ signaling pathway to dictate cell fate and promote proliferation and survival, the role of Pg in these processes is not well understood. Here, we investigate how Pg affects the survival of mouse keratinocytes by challenging both Pg-null cells and their heterozygote counterparts with apoptotic stimuli. Our results indicate that Pg deletion protects keratinocytes from apoptosis, with null cells exhibiting delayed mitochondrial cytochrome c release and activation of caspase-3. Pg-null keratinocytes also exhibit increased messenger RNA and protein levels of the anti-apoptotic molecule Bcl-X-L Compared to heterozygote controls. Importantly, reintroduction of Pg into the null cells shifts their phenotype towards that of the Pg+/- keratinocytes, providing further evidence that Pg plays a direct role in regulating cell survival. Taken together, our results suggest that in addition to its adhesive role in epithelia, Pg may also function in contrast to the prosurvival tendencies of ss-catenin, to potentiate death in cells damaged by apoptotic stimuli, perhaps limiting the potential for the propagation of mutations and cellular transformation.