Novel functions of nuclear transport factors : stress-response mechanism of cell nucleus

不同的细胞应激诱导Importinα的核积聚。然而，目前尚不清楚累积的Importinα是否在细胞核中发挥作用。在这项研究中，我们发现核保留的输入素α2与DNaseI敏感的核成分(S)结合，并选择性上调编码丝氨酸/苏氨酸激酶35(STK35)的基因。染色质免疫沉淀和启动子分析表明，Importinα2与STK35启动子区域结合并促进其转录。此外，STK35蛋白的结构性过表达增强了氧化应激条件下caspase非依赖性细胞的死亡。这些结果表明，核定位的Importinα2影响基因表达，并直接影响细胞命运结果，包括非凋亡性细胞死亡。这是首次有证据表明Importinα在细胞核内具有除核蛋白输入以外的新功能。

Various cellular stresses induce the nuclear accumulation of importinα. However, it is unknown whether accumulated importinαperforms roles in the nucleus. In this study, we found that nuclear-retained importinα2binds with DNase I-sensitive nuclear component(s) and exhibits selective up-regulation of mRNA encoding Serine/ threonine kinase35(STK35). Chromatin immunoprecipitation and promoter analysis demonstrated that importinα2binds to the promoter region of STK35and accelerates its transcription. Furthermore, constitutive overexpression of STK35proteins enhances caspase-independent cell death under oxidative stress conditions. These results reveal that nuclear-localized importinα2influences gene expression and contributes directly to cell fate outcomes including non-apoptotic cell death. This is the first evidence showing that importinαhas novel functions other than nuclear protein import in the nucleus.