文章：

Ezrin去磷酸化/下调参与熊果酸介导的人白血病细胞死亡

Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells

原文发布日期：2013-04-12

DOI: 10.1038/bcj.2013.7

类型: Original Article

开放获取: 是

英文摘要：

Ezrin links the actin filaments with the cell membrane and has a functional role in the apoptotic process. It appears clear that ezrin is directly associated with Fas, leading to activation of caspase cascade and cell death. However, the exact role of ezrin in ursolic acid (UA)-induced apoptosis remains unclear. In this study, we show for the first time that UA induces apoptosis in both transformed and primary leukemia cells through dephosphorylation/downregulation of ezrin, association and polarized colocalization of Fas and ezrin, as well as formation of death-inducing signaling complex. These events are dependent on Rho-ROCK1 signaling pathway. Knockdown of ezrin enhanced cell death mediated by UA, whereas overexpression of ezrin attenuated UA-induced apoptosis. Our in vivo study also showed that UA-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with the dephosphorylation/downregulation of ezrin. Such findings suggest that the cytoskeletal protein ezrin may represent an attractive target for UA-mediated lethality in human leukemia cells.

摘要翻译： 

埃兹蛋白将肌动蛋白丝与细胞膜连接起来，并在细胞凋亡过程中发挥功能性作用。目前明确的是，埃兹蛋白直接与Fas受体结合，导致 caspase 级联反应激活和细胞死亡。然而，埃兹蛋白在熊果酸（UA）诱导的细胞凋亡中的具体作用仍不清楚。本研究首次表明，UA通过埃兹蛋白的去磷酸化/下调、Fas与埃兹蛋白的结合及极化共定位以及死亡诱导信号复合体的形成，诱导转化细胞和原代白血病细胞发生凋亡。这些过程依赖于Rho-ROCK1信号通路。敲低埃兹蛋白增强了UA介导的细胞死亡，而过表达埃兹蛋白则减弱了UA诱导的细胞凋亡。我们的体内研究还显示，UA抑制小鼠白血病异种移植模型肿瘤生长的作用与埃兹蛋白的去磷酸化/下调相关。这些发现表明，细胞骨架蛋白埃兹蛋白可能成为UA介导人类白血病细胞杀伤作用的一个有吸引力的靶点。

原文链接：

Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells