Nuclear transport of peroxisome-proliferator activated receptor α.
Nuclear transport of peroxisome-proliferator activated receptor α.
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DOI：
10.1093/jb/mvq144
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发表时间：
2011-03
影响因子：
2.7
通讯作者：
F. Iwamoto;Tomoe Umemoto;K. Motojima;Y. Fujiki
中科院分区：
文献类型：
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作者：
F. Iwamoto;Tomoe Umemoto;K. Motojima;Y. Fujiki
过氧化物酶体增殖物激活受体α(PPARα)是一种配体激活的转录因子，在包括脂质代谢在内的几个重要途径中发挥关键作用。尽管PPARα的核定位对其反式激活活性是必不可少的，但PPARα在细胞内的运输机制仍不清楚。我们在这里识别和表征了位于PPARα的DNA结合区和铰链区之间的核定位信号。NLS由两个碱性氨基酸簇组成，位于序列中，包含144-187位的氨基酸残基。我们的突变分析表明，这种NLS中的碱性残基是核进口所必需的。此外，PPARDNA NLS以一种独立于α结合活性的方式与著名的核转运蛋白Importinα和Importinβ结合。
Peroxisome-proliferator activated receptor α (PPARα) is a ligand-activated transcription factor, playing a key role in several essential pathways including lipid metabolism. Although nuclear localization of PPARα is essential for its transactivation activity, mechanisms underlying intracellular traffics of PPARα remain undefined. We here identify and characterize a nuclear localization signal (NLS) residing in the junction between DNA-binding domain and hinge regions of PPARα. The NLS consists of two basic-amino acid clusters locating in the sequence encompassing amino acid residues at 144-187. We evidently show by mutational analysis that the basic residues in this NLS are essential for the nuclear import. Moreover, the PPARα NLS binds well-known nuclear transporters, importin α and importin β, in a manner independent of DNA-binding activity.