Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development.
Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development.
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DOI：
10.1093/glycob/cwj096
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发表时间：
2006-06
期刊：
影响因子：
4.3
通讯作者：
T. Whisenhunt;Xiaoyong Yang;Damon B. Bowe;A. Paterson;B. V. Van Tine;J. Kudlow
中科院分区：
文献类型：
--
作者：
T. Whisenhunt;Xiaoyong Yang;Damon B. Bowe;A. Paterson;B. V. Van Tine;J. Kudlow
虽然核蛋白和细胞质蛋白被N-乙酰葡糖胺修饰的知识已经存在了几十年，但直到最近才显示出其功能。现在有大量的数据强调了在多个细胞过程中适当调节这种修饰的重要性。目前，已知只有两种酶调节这种修饰。O-GlcNAc转移酶（OGT）通过添加N-乙酰葡糖胺后修饰蛋白质底物。双功能核/胞质O-GlcNAc酶和乙酰转移酶（NCOAT）负责从靶蛋白切割修饰。在这里，我们首次证明了这两种相反的酶到一个单一的O-GlcNAczyme复合物的一个不寻常的协会。NCOAT和OGT通过特定的结构域紧密结合，使得NCOAT伴随OGT与组蛋白脱乙酰酶（HDAC）一起形成转录共抑制复合物。从OGT关联中排除NCOAT活性阻断了转基因小鼠中适当的雌激素依赖性细胞信号传导以及乳腺发育。这表明，该委员会处于战略地位，可以迅速对付海外工作人员和人道主义援助协调员，而不需要征聘该委员会。
Although the knowledge that nuclear and cytoplasmic proteins are modified with N-acetylglucosamine has existed for decades, little has been shown as to its function until recently. There are now substantial data highlighting the significance of proper regulation of this modification in multiple cellular processes. Currently, only two enzymes are known that regulate this modification. O-GlcNAc transferase (OGT) modifies protein substrates posttranslationally by adding the N-acetylglucosamine. Bifunctional nuclear/cytoplasmic O-GlcNAcase and acetyl transferase (NCOAT) is responsible for cleaving the modification from target proteins. Here, we demonstrate for the first time an unusual association of these two opposing enzymes into a single O-GlcNAczyme complex. NCOAT and OGT associate strongly through specific domains such that NCOAT accompanies OGT, with histone deacetylases (HDACs), into transcription corepression complexes. Exclusion of NCOAT activities from OGT association blocks proper estrogen-dependent cell signaling as well as mammary development in transgenic mice. This demonstrates that NCOAT is in a strategic position to rapidly counteract OGT and HDAC without requiring its recruitment.