Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase
Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase
复制标题
核因子-erythroid-2 相关转录因子-1 (Nrf1) 受 O-GlcNAc 转移酶调节
DOI：
10.1016/j.freeradbiomed.2017.06.008
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发表时间：
2017-09-01
影响因子：
7.4
通讯作者：
Chan, Jefferson Y.
中科院分区：
文献类型：
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作者：
Han, Jeong Woo;Valdez, Joshua L.;Chan, Jefferson Y.
核因子E2相关因子1(Nrf1)转录因子在调节细胞内稳态方面起着关键作用。用蛋白质组学的方法，我们确定宿主细胞因子-1(HCF1)和O-GlcNAc转移酶(OGT)是Nrf1的一个亚型，Nrf1a是Nrf1的一个亚型。NRF1a通过HCF1结合基序(HBM)直接与HCF1相互作用，而与OGT的相互作用是通过HCF1介导的。HCF1和OGT的过表达导致Nrf1a蛋白稳定性增加。O-GlcNAc的加入减少了Nrf1a的泛素化和降解。OGT过表达和PUGNAc处理可增加Nrf1a的转录激活。综上所述，这些数据表明OGT可以作为Nrf1a的调节因子。
The Nrf1 (Nuclear factor E2-related factor 1) transcription factor performs a critical role in regulating cellular homeostasis. Using a proteomic approach, we identified Host Cell Factor-1 (HCF1), a co-regulator of transcription, and O-GlcNAc transferase (OGT), the enzyme that mediates protein O-GlcNAcylation, as cellular partners of Nrf1a, an isoform of Nrf1. Nrf1a directly interacts with HCF1 through the HCF1 binding motif (HBM), while interaction with OGT is mediated through HCF1. Overexpression of HCF1 and OGT leads to increased Nrf1a protein stability. Addition of O-GlcNAc decreases ubiquitination and degradation of Nrf1a. Transcriptional activation by Nrf1a is increased by OGT overexpression and treatment with PUGNAc. Together, these data suggest that OGT can act as a regulator of Nrf1a.