Department of Laboratory Medicine and Pathology, University of California, Irvine, D440 Medical Sciences, Irvine, CA 92697, USA.
Departments of Physiology and Biophysics, University of California, Irvine, D440 Medical Sciences, Irvine, CA 92697, USA.
Free Radic Biol Med. 2017 Sep;110:196-205. doi: 10.1016/j.freeradbiomed.2017.06.008. Epub 2017 Jun 15.
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.
Nrf1（核因子 E2 相关因子 1）转录因子在调节细胞内稳态方面起着关键作用。我们使用蛋白质组学方法鉴定了转录共调节剂 Host Cell Factor-1（HCF1）和介导蛋白质 O-GlcNAc 化的酶 O-GlcNAc 转移酶（OGT），它们是 Nrf1a（Nrf1 的一种同工型）的细胞伴侣。Nrf1a 通过 HCF1 结合基序（HBM）直接与 HCF1 相互作用，而与 OGT 的相互作用则通过 HCF1 介导。HCF1 和 OGT 的过表达导致 Nrf1a 蛋白稳定性增加。O-GlcNAc 的添加可减少 Nrf1a 的泛素化和降解。OGT 的过表达和 PUGNAc 的处理增加了 Nrf1a 的转录激活。总之，这些数据表明 OGT 可以作为 Nrf1a 的调节剂。
