RFNG,也称为Radical Fringe,是一种重要的N-乙酰氨基葡萄糖转移酶,属于Fringe家族成员之一。Fringe家族成员包括Lunatic Fringe (LFNG), Manic Fringe (MFNG) 和 Radical Fringe (RFNG)。RFNG通过将N-乙酰氨基葡萄糖转移到Notch受体的O-连接岩藻糖上,调节Notch信号通路,从而影响细胞分化、发育、代谢和疾病发生。
RFNG在多种疾病中发挥重要作用,包括结直肠癌和胰腺癌。在结直肠癌中,RFNG的磷酸化导致其核转位,从而抑制p53的磷酸化和CDKN1A的表达,增加SLC7A11的表达,抑制细胞凋亡和铁死亡,从而增强结直肠癌对化疗药物奥沙利铂的耐药性[1]。在胰腺癌中,RFNG的高表达与患者总生存期差密切相关,且LFNG的表达水平与预后呈负相关[2]。
此外,RFNG还与多种疾病的发生和发展有关。RFNG可以影响NOTCH3的降解和信号传导,从而影响血管平滑肌细胞的发育和存活,与CADASIL的发生和发展有关[3]。RFNG还可以与Rac3b和sgca基因形成调控簇,参与后脑边界的形成[4]。RFNG还参与T和B细胞的发育,缺乏RFNG会导致T和B细胞发育受损[5]。
综上所述,RFNG是一种重要的N-乙酰氨基葡萄糖转移酶,通过调节Notch信号通路影响多种生物学过程。RFNG在多种疾病中发挥重要作用,包括结直肠癌、胰腺癌、CADASIL和T/B细胞发育。RFNG的研究有助于深入理解Notch信号通路的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Di, Yuqin, Zhang, Xiang, Wen, Xiangqiong, Wang, Ziyang, He, Weiling. 2024. MAPK Signaling-Mediated RFNG Phosphorylation and Nuclear Translocation Restrain Oxaliplatin-Induced Apoptosis and Ferroptosis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2402795. doi:10.1002/advs.202402795. https://pubmed.ncbi.nlm.nih.gov/39120977/
2. Gong, Xun, Zheng, Chenglong, Jia, Haiying, Li, Xiaowu, Liu, Yuchen. 2023. A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment. In BMC cancer, 23, 1065. doi:10.1186/s12885-023-11545-3. https://pubmed.ncbi.nlm.nih.gov/37932706/
3. Suzuki, Shodai, Mashiko, Taiki, Tsukamoto, Yohei, Okajima, Tetsuya, Itoh, Motoyuki. 2024. The N-acetylglucosaminyltransferase Radical fringe contributes to defects in JAG1-dependent turnover and signaling of NOTCH3 CADASIL mutants. In The Journal of biological chemistry, 300, 107787. doi:10.1016/j.jbc.2024.107787. https://pubmed.ncbi.nlm.nih.gov/39303912/
4. Letelier, Joaquín, Terriente, Javier, Belzunce, Ivan, Martínez-Morales, Juan R, Pujades, Cristina. 2018. Evolutionary emergence of the rac3b/rfng/sgca regulatory cluster refined mechanisms for hindbrain boundaries formation. In Proceedings of the National Academy of Sciences of the United States of America, 115, E3731-E3740. doi:10.1073/pnas.1719885115. https://pubmed.ncbi.nlm.nih.gov/29610331/
5. Song, Yinghui, Kumar, Vivek, Wei, Hua-Xing, Qiu, Ju, Stanley, Pamela. 2015. Lunatic, Manic, and Radical Fringe Each Promote T and B Cell Development. In Journal of immunology (Baltimore, Md. : 1950), 196, 232-43. doi:10.4049/jimmunol.1402421. https://pubmed.ncbi.nlm.nih.gov/26608918/