Nfe2l2,也称为Nrf2(nuclear factor, erythroid derived 2, like 2),是一种重要的转录因子,参与调节细胞内抗氧化基因的表达,以响应氧化应激等压力条件。Nfe2l2在维持细胞内氧化还原稳态和蛋白质稳态方面发挥着关键作用。Nfe2l2通过与特定的DNA序列结合,激活或抑制下游基因的表达,从而调节细胞的生物学过程。例如,研究发现Nfe2l2可以与LAMP2基因的特定序列结合,影响LAMP2A蛋白的表达水平,进而调节伴侣介导的自噬(CMA)活性[1]。此外,Nfe2l2还与肿瘤的发生发展密切相关。研究发现,Nfe2l2的基因多态性与结核病的易感性相关[2]。Nfe2l2的突变与食管鳞状细胞癌的不良预后相关[3,4,5]。Nfe2l2的激活可以促进肿瘤的发生发展,而Nfe2l2的抑制可以抑制肿瘤的生长[6]。此外,Nfe2l2还与线粒体和核之间的通讯有关。研究发现,线粒体编码的MOTS-c肽可以转移到细胞核,并与Nfe2l2等转录因子相互作用,调节核基因的表达[7]。总之,Nfe2l2是一种重要的转录因子,在维持细胞内氧化还原稳态和蛋白质稳态、肿瘤的发生发展以及线粒体和核之间的通讯等方面发挥着重要作用。深入研究Nfe2l2的生物学功能和调控机制,有助于揭示相关疾病的发病机制,为疾病的治疗和预防提供新的思路和策略。
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3. Kim, Kyung Hwa, Son, Jyung Mean, Benayoun, Bérénice A, Lee, Changhan. 2018. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. In Cell metabolism, 28, 516-524.e7. doi:10.1016/j.cmet.2018.06.008. https://pubmed.ncbi.nlm.nih.gov/29983246/
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