Ras-Raf signaling needs prohibitin
Ras-Raf signaling needs prohibitin
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DOI：
10.4161/cc.4.11.2142
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发表时间：
2005-11-01
期刊：
影响因子：
4.3
通讯作者：
Rudel, T
中科院分区：
文献类型：
--
作者：
Rajalingam, K;Rudel, T
Prohibitin与多种细胞功能有关，包括细胞周期控制、衰老、凋亡和线粒体蛋白的稳定。通过采用使用siRNA的功能丧失方法，我们已经证明了PHB在活性Ras激活Raf/MEK/ERK通路和调节上皮细胞粘附和迁移中的意想不到的作用。PHB直接与C-Raf相互作用，并且是活性Ras从C-Raf置换14-3-3以促进质膜定位和活化所必需的。此外，粘附复合蛋白钙粘蛋白和β-连环蛋白定位于质膜，表明PHB沉默细胞中粘附连接稳定。我们的研究结果表明，在控制一个中央信号通路参与细胞生长和恶性转化的PHB的功能。
Prohibitin has been connected to diverse cellular functions including cell cycle control, senescence, apoptosis and stabilization of mitochondrial proteins. By employing a loss of function approach using siRNAs we have demonstrated an unexpected role of PHB in the activation of Raf/MEK/ERK pathway by active Ras and in modulating epithelial cell adhesion and migration. PHB directly interacts with C-Raf and is required for the displacement of 14-3-3 from C-Raf by active Ras to facilitate plasma membrane localization and activation. Further, the adherent complex proteins cadherin and beta-catenin were localized to plasma membrane suggesting stabilized adherent junctions in PHB silenced cells. Our findings demonstrated a function of PHB in the control of a central signaling pathway involved in cell growth and malignant transformation.