Transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status
Transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status
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转录因子 Nrf1 受其 O-GlcNAcNA 酰化状态的负调节
DOI：
10.1016/j.febslet.2015.07.030
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发表时间：
2015-08-19
期刊：
影响因子：
3.5
通讯作者：
Zhang, Yiguo
中科院分区：
文献类型：
--
作者：
Chen, Jiayu;Liu, Xiping;Zhang, Yiguo
O-连接N-乙酰氨基葡萄糖转移酶(OGT)是一种与Nrf1相互作用的蛋白。在这里，我们证明了Nrf1能够与OGT相互作用，他们的免疫共沉淀物被酶O-GlcN酰化。可能的O-GlcN酰化负调控Nrf1/TCF11，降低其蛋白质稳定性和靶基因表达的反式激活活性。OGT的过表达促进了Cnc-bZIP蛋白的泛素化，促进了Nrf1的周转。此外，OGT还证实了Nrf1中富含丝氨酸/茶氨酸的PEST2降解子序列参与了蛋白质O-GlcN酰化。总体而言，Nrf1受其O-GlcN酰化状态的负调控，而O-GlcN酰化状态取决于葡萄糖浓度。(C)2015年欧洲生化学会联合会。爱思唯尔出版，版权所有。
O-Linked N-acetylglucosatnine transferase (OGT) was identified as an Nrf1-interacting protein. Herein, we show that Nrf1 enables interaction with OGT and their co-immunoprecipitates are O-GlcNAcylated by the enzyme. The putative O-GlcNAcylation negatively regulates Nrf1/TCF11 to reduce both its protein stability and transactivation activity of target gene expression. The turnover of Nrf1 is enhanced upon overexpression of OGT, which promotes ubiquitination of the CNC-bZIP protein. Furthermore, the serine/theorine-rich sequence of PEST2 degron within Nrf1 is identified to be involved in the protein O-GlcNAcylation by OGT. Overall, Nrf1 is negatively regulated by its O-GlcNAcylation status that depends on the glucose concentrations. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.