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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Evolution of Na,K-ATPase βm-subunit into a coregulator of transcription in placental mammals
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Evolution of Na,K-ATPase βm-subunit into a coregulator of transcription in placental mammals

机译：Na，K-ATPaseβm亚基向胎盘哺乳动物转录共调节子的进化

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摘要

Change in gene functions (gene cooption) is one of the key mechanisms of molecular evolution. Genes can acquire new functions via alteration in properties of encoded proteins and/or via changes in temporal or spatial regulation of expression. Here we demonstrate radical changes in the functions of orthologous ATP1B4 genes during evolution of vertebrates. Expression of ATP1B4 genes is brain-specific in teleost fishes, whereas it is predominantly muscle-specific in tetrapods. The encoded βm-proteins in fish, amphibian, and avian species are β-subunits of Na,K-ATPase located in the plasma membrane. In placental mammals βm-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). Through interaction with SKIP, eutherian βm acquired new functions as exemplified by regulation of TGF-β-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-β signaling. Thus, orthologous vertebrate ATP1B4 genes represent an instance of gene cooption that created fundamental changes in the functional properties of the encoded proteins.
机译：基因功能的改变（基因共选项）是分子进化的关键机制之一。基因可以通过改变编码蛋白质的性质和/或通过改变表达的时间或空间调控来获得新功能。在这里，我们证明了脊椎动物进化过程中直系同源ATP1B4基因功能的根本变化。 ATP1B4基因的表达在硬骨鱼类中是大脑特异性的，而在四足动物中主要是肌肉特异性的。鱼，两栖动物和鸟类中编码的βm蛋白是位于质膜上的Na，K-ATPase的β亚基。在胎盘哺乳动物中，βm蛋白失去其祖先功能，在围产期心肌细胞的核膜中积累，并与转录共调节因子Ski-interacting蛋白（SKIP）结合。通过与SKIP的相互作用，以太网βm获得了新功能，例如调节TGF-β反应性报道分子和增加TGF-β信号抑制剂Smad7的mRNA水平。因此，直系同源的脊椎动物ATP1B4基因代表了基因共选项的一个实例，该基因在编码蛋白的功能特性中产生了根本性的变化。

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