Characteristic increase in nucleocytoplasmic protein glycosylation by O-GlcNAc in 3T3-L1 adipocyte differentiation
Characteristic increase in nucleocytoplasmic protein glycosylation by O-GlcNAc in 3T3-L1 adipocyte differentiation
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DOI：
10.1016/j.bbrc.2010.06.105
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发表时间：
2010-07-30
影响因子：
3.1
通讯作者：
Kamemura, Kazuo
中科院分区：
文献类型：
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作者：
Ishihara, Katsunori;Takahashi, Isao;Kamemura, Kazuo
核质蛋白的O-连接的β-N-乙酰葡糖胺化（O-GlcNAc ylation）是目前研究的多细胞生物中普遍存在的翻译后修饰。由于异常的O-GlcNAc化与胰岛素抵抗有关，因此确定O-GlcNAc化在间充质细胞如前脂肪细胞的分化中的状态是重要的。在这项研究中，我们发现在小鼠3 T3-L1前脂肪细胞中O-GlcNAc化水平的分化依赖性急剧增加。与C/EBP α表达相关的O-GlcNAc化增加的发生部分是由于O-GlcNAc转移酶表达增加。除了众所周知的O-GlcNAc酰化蛋白质如核孔蛋白和波形蛋白外，丙酮酸羧化酶、长链脂肪酸-CoA连接酶1和尤文肉瘤蛋白被鉴定为随着脂肪细胞分化而被高度O-GlcNAc酰化的蛋白质。脂肪细胞分化和O-GlcNAc化的分化依赖性增加均被6-重氮-5-氧代正亮氨酸阻断。这些结果表明，O-GlcNAc酰化参与，至少部分，在脂肪形成。(C)2010年爱思唯尔公司All rights reserved.
O-Linked beta-N-acetylglucosaminylation (O-GlcNAcylation) of nucleocytoplasmic proteins is a ubiquitous post-translational modification in multicellular organisms studied so far. Since aberrant O-GlcNAcylation has a link with insulin resistance, iris important to establish the status of O-GIcNAcylation in differentiation of mesenchymal cells such as preadipocytes. In this study, we found a differentiation-dependent drastic increase in the level of O-GIcNAcylation in mouse 3T3-L1 preadipocytes. The occurrence of the increase in O-GIcNAcylation, which correlated with the expression of C/EBP alpha, was in part due to increased expression of O-GlcNAc transferase. In addition to the well-known O-GlcNAcylated proteins such as nucleoporins and vimentin, pyruvate carboxylase, long chain fatty acid-CoA ligase 1, and Ewing sarcoma protein were identified as the proteins which are heavily O-GlcNAcylated with the adipocyte differentiation. Both adipocyte differentiation and the differentiation-dependent increase in O-GIcNAcylation were blocked by 6-diazo-5-oxo-norleucine. These results suggest that O-GIcNAcylation particilates, at least in part, in adipogenesis. (C) 2010 Elsevier Inc. All rights reserved.