Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells.
Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells.
复制标题
DOI：
10.1038/bcj.2013.7
复制
发表时间：
2013-04-12
影响因子：
12.8
通讯作者：
Gao, N.
中科院分区：
文献类型：
--
作者：
Li, G.;Zhou, T.;Liu, L.;Chen, J.;Zhao, Z.;Peng, Y.;Li, P.;Gao, N.
Ezrin将肌动蛋白细丝与细胞膜联系在一起，并在细胞凋亡过程中发挥作用。很明显，Ezrin与Fas直接相关，导致caspase级联激活和细胞死亡。然而，Ezrin在熊果酸(UA)诱导的细胞凋亡中的确切作用仍不清楚。在这项研究中，我们首次证明UA通过Ezrin的去磷酸化/下调、Fas和Ezrin的结合和极化共定位以及死亡诱导信号复合体的形成来诱导转化和原代白血病细胞的凋亡。这些事件依赖于Rho-ROCK1信号通路。Ezrin基因敲除增强了UA介导的细胞死亡，而过表达Ezrin则减弱了UA诱导的细胞凋亡。我们的体内研究还表明，UA介导的抑制小鼠白血病移植瘤模型的肿瘤生长与Ezrin的去磷酸化/下调有关。这些发现表明，细胞骨架蛋白Ezrin可能是UA介导的人类白血病细胞致死的一个有吸引力的靶点。
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.
登录
查看更多内容
影响因子：
3.3
作者：
Morelli, A;Chiozzi, P;Di Virgilio, F
通讯作者：
Di Virgilio, F
DOI：
10.1186/bcr1006
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Elliott BE;Meens JA;SenGupta SK;Louvard D;Arpin M
通讯作者：
Arpin M
影响因子：
11.4
作者：
Pust, S;Morrison, H;Herrlich, P
通讯作者：
Herrlich, P
影响因子：
11.4
作者：
Chakrabandhu, Krittalak;Herincs, Zoltan;Hueber, Anne-Odile
通讯作者：
Hueber, Anne-Odile
影响因子：
20.3
作者：
Monni, Richard;Haddaoui, Lamya;Moreau-Gachelin, Francoise
通讯作者：
Moreau-Gachelin, Francoise