Diversification of importin-α isoforms in cellular trafficking and disease states.
Diversification of importin-α isoforms in cellular trafficking and disease states.
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DOI：
10.1042/bj20141186
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发表时间：
2015-02-15
期刊：
影响因子：
--
通讯作者：
Cingolani G
中科院分区：
文献类型：
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作者：
Pumroy RA;Cingolani G
人类基因组编码输入蛋白α的七种亚型，分为三个亚家族，称为α1，α2和α3。所有同种型共享基本上保守的结构，其由N-末端、自抑制的输入蛋白-β-结合（伊布）结构域和与核定位信号（NLS）货物缔合的C-末端臂（Armadillo）-核心组成。尽管在氨基酸序列和三维结构上惊人的相似性，importin-α异构体在体内显示出显着的底物特异性。在本综述中，我们着眼于importin-α亚型之间的关键差异，并提供了一个全面的库存已知的病毒和细胞货物，已被证明优先与特定的亚型。我们阐明了衔接子输入素α如何多样化为7种亚型，从而扩大了核质转运的动态范围和调控，为药理学干预提供了意想不到的机会。新出现的观点认为输入素α是一种关键的信号分子，其亚型赋予与人类疾病直接相关的病毒和细胞货物优先进入核和时空特异性。
The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases.