HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell Growth.
HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell Growth.
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DOI：
10.1155/2012/426138
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发表时间：
2012
影响因子：
--
通讯作者：
Nose K
中科院分区：
文献类型：
--
作者：
Shibanuma M;Mori K;Nose K
HIC-5 是一种与桩蛋白同源的多域 LIM 蛋白，充当粘着斑和细胞核中的分子支架。它与仅 LIM 蛋白、PINCH 和 CRP2 形成移动分子单元，并通过核输出信号 (NES) 进出细胞核。值得注意的是，HIC-5 的 NES 的独特之处在于其对细胞氧化还原状态的敏感性。最近，HIC-5 的移动单元被认为参与细胞生长贴壁依赖性的调节。当粘附力丧失时，细胞中活性氧的增加会改变 NES 并停止穿梭，从而导致细胞周期控制。更具体地说，该系统规避了细胞周期蛋白 D1 的核定位并反式激活分离细胞中的 p21Cip1，从而避免了贴壁依赖性细胞生长。因此，HIC-5-LIM 唯一的蛋白质复合物已成为调节细胞生长的锚定依赖性的自动防故障系统。
HIC-5 is a multidomain LIM protein homologous to paxillin that serves as a molecular scaffold at focal adhesions and in the nucleus. It forms mobile molecular units with LIM-only proteins, PINCH, and CRP2 and translocates in and out of the nucleus via a nuclear export signal (NES). Of note, NES of HIC-5 is distinctive in its sensitivity to the cellular redox state. Recently, the mobile units of HIC-5 have been suggested to be involved in the regulation of the anchorage dependence of cell growth. On loss of adhesion, an increase in reactive oxygen species in the cells modifies NES and stops shuttling, which leads to cell-cycle control. More specifically, the system circumvents nuclear localization of cyclin D1 and transactivates p21Cip1 in detached cells, thereby avoiding anchorage-independent cell growth. Thus, the HIC-5-LIM only protein complex has emerged as a fail-safe system for regulating the anchorage dependence of cell growth.