Miyamoto Yoichi, Loveland Kate L, Yoneda Yoshihiro
Commun Integr Biol. 2012 Mar 1;5(2):220-2. doi: 10.4161/cib.19194.
Importin α is recognized as a classical nuclear localization signal (cNLS) receptor which mediates nucleocytoplasmic transport. However, it rapidly accumulates in the nucleus in response to cellular stresses, including oxidative stress, causing a blockade of the classical nuclear import pathway. We set out to determine whether importin α performs roles in the nucleus after cellular exposure to stresses and discovered that it can act directly to modulate gene expression. With remarkable selectivity, importin α2 can access the promoter of Serine/threonine kinase 35 (STK35) and increase the levels of this transcript without requirement for importin β1. The nuclear accumulation of importin α occurred following exposure to stresses which decreased intracellular ATP levels and was followed by non-apoptotic cell death. Hence the gene regulatory function of nuclear importin α can direct cell fate. There are now several reports of nuclear-localized importin α proteins in diverse cellular states, including cancer. Here we discuss the physiological significance of this novel functional capacity of nuclear importin α relationship to a variety of cellular states and fates.
输入蛋白α被认为是一种经典的核定位信号（cNLS）受体，介导核质运输。然而，它会在包括氧化应激在内的细胞应激反应中迅速在细胞核中积累，导致经典核输入途径受阻。我们着手确定细胞暴露于应激后输入蛋白α在细胞核中是否发挥作用，并发现它可以直接调节基因表达。输入蛋白α2具有显著的选择性，能够进入丝氨酸/苏氨酸激酶35（STK35）的启动子区域，并在无需输入蛋白β1的情况下增加该转录本的水平。输入蛋白α在暴露于降低细胞内ATP水平的应激后会在细胞核中积累，随后发生非凋亡性细胞死亡。因此，细胞核中输入蛋白α的基因调控功能可以决定细胞命运。现在有几篇报道称，在包括癌症在内的多种细胞状态下都存在核定位的输入蛋白α蛋白。在此，我们讨论核输入蛋白α这种新功能能力与多种细胞状态和命运相关的生理意义。
