Quantitative regulation of nuclear pore complex proteins by O-GlcNAcylation
Quantitative regulation of nuclear pore complex proteins by O-GlcNAcylation
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DOI：
10.1016/j.bbamcr.2013.06.008
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发表时间：
2013-12-01
影响因子：
5.1
通讯作者：
Yoneda, Yoshihiro
中科院分区：
文献类型：
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作者：
Mizuguchi-Hata, Chiaki;Ogawa, Yutaka;Yoneda, Yoshihiro
核孔复合物（NPC）是由大约30种不同的蛋白质组成的大分子组装体，称为核孔蛋白。几种核孔蛋白是O-GlcNAc化的，这是一种翻译后修饰，其中单糖β-N-乙酰葡糖胺（GlcNAc）连接到蛋白质内的丝氨酸或苏氨酸残基上。然而，这种修饰对核孔蛋白的生物学意义仍然不清楚。在这里，我们发现，Nup 62和Nup 88蛋白水平显着下降后敲低的O-GlcNAc转移酶（OGT），催化O-GlcNAc酰化的细胞内蛋白质。尽管Nup 88不像Nup 62那样不被抗O-GlcNAc抗体或WGA-HRP识别，但Nup 62的敲低引起Nup 88蛋白水平的降低，表明在OGT敲低的细胞中观察到的Nup 88的降低是由于Nup 62的降低。此外，我们发现Nup 88与非O-G1 cNAc酰化Nup 62相比优先与O-G1 cNAc酰化Nup 62结合。这些结果表明，Nup 62蛋白水平主要通过O-GlcNAc酰化来维持，Nup 88通过其与O-GlcNAc酰化Nup 62的相互作用来定量调节。(c)2013爱思唯尔有限公司版权所有。
The nuclear pore complex (NPC) is a macromolecular assembly consisting of approximately 30 different proteins called nucleoporins. Several nucleoporins are O-GIcNAcylated, which is a post-translational modification in which the monosaccharide beta-N-acetylglucosamine (GlcNAc) is attached to serine or threonine residues within proteins. However, the biological significance of this modification on nucleoporins remains obscure. Here we found that Nup62 and Nup88 protein levels were significantly decreased upon knockdown of O-GlcNAc transferase (OGT), which catalyzes the O-GlcNAcylation of intracellular proteins. Although Nup88, unlike Nup62, was not recognized by an anti-O-GlcNAc antibody or WGA-HRP, knockdown of Nup62 caused a reduction in Nup88 protein levels, suggesting that the observed decrease in Nup88 in OGT knocked-down cells is due to a decrease in Nup62. Furthermore, we found that Nup88 was preferentially associated with O-GlcNAcylated Nup62 compared with non-O-G1cNAcylated Nup62. These results indicate that Nup62 protein levels are primarily maintained by O-GIcNAcylation and that Nup88 is quantitatively regulated through its interaction with O-GlcNAcylated Nup62. (c) 2013 Elsevier B.V. All rights reserved.