Guerrero-Santoro Jennifer, Yang Lan, Stallcup Michael R, DeFranco Donald B
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Cell Biochem. 2004 Jul 1;92(4):810-9. doi: 10.1002/jcb.20109.
Hydrogen peroxide-inducible clone-5 (Hic-5), belongs to the group III LIM domain protein family and contains four carboxyl-terminal LIM domains (LIM1-LIM4). In addition to its role in focal adhesion signaling, Hic-5 acts in the nucleus as a coactivator for some steroid hormone receptors such as the glucocorticoid receptor (GR) and androgen receptor (AR). Based upon its effect on AR transactivation, Hic-5 has also been designated as ARA55. Here, we report mapping studies of Hic-5/ARA55 functional domains and establish that LIM3 and LIM4 are necessary for maximal effects on GR transactivation. However, results from yeast two-hybrid assays demonstrated that these two LIM domains together, while necessary, are not sufficient to interact with the tau2 transactivation domain of GR. LIM4 also functions as a nuclear matrix targeting sequence (NMTS) for Hic-5/ARA55, as it is both necessary and sufficient to target a heterologous protein to the nuclear matrix. Thus, as suggested from previous analysis of LIM domain-containing proteins, separate but highly related LIM domains serve distinct functions.
过氧化氢诱导克隆-5（Hic-5）属于III组LIM结构域蛋白家族，包含四个羧基末端LIM结构域（LIM1-LIM4）。除了在粘着斑信号传导中的作用外，Hic-5在细胞核中作为一些类固醇激素受体（如糖皮质激素受体（GR）和雄激素受体（AR））的共激活因子发挥作用。基于其对AR反式激活的作用，Hic-5也被命名为ARA55。在此，我们报告了Hic-5/ARA55功能结构域的定位研究，并确定LIM3和LIM4对GR反式激活的最大效应是必需的。然而，酵母双杂交试验的结果表明，这两个LIM结构域虽然是必需的，但不足以与GR的tau2反式激活结构域相互作用。LIM4还作为Hic-5/ARA55的核基质靶向序列（NMTS）发挥作用，因为它对于将异源蛋白靶向核基质既是必需的也是充分的。因此，正如先前对含LIM结构域蛋白的分析所表明的那样，单独但高度相关的LIM结构域发挥着不同的功能。
