Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation
Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation
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DOI：
10.1038/sj.emboj.7601845
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发表时间：
2007-10-17
期刊：
影响因子：
11.4
通讯作者：
Guerini, Danilo
中科院分区：
文献类型：
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作者：
Golks, Alexander;Tran, Thi-Thanh Thao;Guerini, Danilo
通过O-连接的N-乙酰葡糖胺转移酶（OGT）用O-连接的β-N-乙酰葡糖胺（O-GlcNAc）对核和细胞质蛋白的动态修饰是响应于各种刺激的调节性翻译后修饰。在这里，我们证明了OGT是T和B淋巴细胞活化的中心因素。siRNA介导的T细胞中OGT的敲低导致转录因子NFAT和NF κ B的活化受损。这导致IL-2产生的减少与T细胞活化的预防一致。通过刺激B细胞受体介导的B细胞的早期活化也需要OGT。从机制上讲，我们证明了NF κ B以及NFAT在直接结合OGT后被O-GlcNAc糖基化。此外，动力学实验表明，O-GlcNAc修饰显着增加淋巴细胞活化后不久，它可能是所需的核转位的转录因子NF κ B和NFAT。
The dynamic modification of nuclear and cytoplasmic proteins with O-linked beta-N-acetylglucosamine (O-GlcNAc) by the O-linked N-acetylglucosaminyltransferase (OGT) is a regulatory post-translational modification that is responsive to various stimuli. Here, we demonstrate that OGT is a central factor for T- and B-lymphocytes activation. SiRNA-mediated knockdown of OGT in T cells leads to an impaired activation of the transcription factors NFAT and NF kappa B. This results in a reduction of IL-2 production consistent with prevention of T- cell activation. OGT is also required for the early activation of B cells mediated by stimulation of the B-cell receptor. Mechanistically, we demonstrate that NF kappa B as well as NFAT are glycosylated with O-GlcNAc after direct binding to OGT. Moreover, kinetic experiments show that O-GlcNAc modification prominently increased shortly after activation of lymphoid cells and it might be required for nuclear translocation of the transcription factors NF kappa B and NFAT.