核因子红细胞2相关因子2与癌症发展中的自噬调节
Nuclear factor erythroid 2-related factor 2 and autophagy regulation in cancer development.
作者信息
Dornas Waleska
机构信息
Department of Biochemistry, Center for Cellular and Molecular Therapy, Universidade Federal de São Paulo, São Paulo, SP Brazil.
出版信息
Biophys Rev. 2022 Aug 12;14(5):1105-1107. doi: 10.1007/s12551-022-00992-0. eCollection 2022 Oct.
Nuclear factor erythroid 2-related factor 2 (Nrf2) mitigates cell damage due to stress, environmental xenobiotics, and toxic chemicals. Nrf2 is present in the cytoplasm bound to its cysteine-rich Kelch domain-containing partner, Kelch-like ECH-associated protein 1 (Keap1), where is ubiquitinated and degraded. In addition to inducers that disrupt the Keap1-Nrf2 complex, defective autophagy has recently been shown to upregulate endogenous p62, which interacts with Keap1 triggering transcriptional activation of Nrf2 in several cancers. This regulation by Nrf2-dependent transactivation of cytoprotective genes needs to be validated by clinical trials in view of its persistent activation in a p62-dependent manner when there is deregulation of autophagy.
核因子红细胞2相关因子2（Nrf2）可减轻因应激、环境外源性物质和有毒化学物质导致的细胞损伤。Nrf2存在于细胞质中，与富含半胱氨酸的含Kelch结构域的伴侣蛋白—— Kelch样ECH相关蛋白1（Keap1）结合，在那里它会被泛素化并降解。除了破坏Keap1-Nrf2复合物的诱导剂外，最近还发现自噬缺陷会上调内源性p62，p62与Keap1相互作用，在几种癌症中触发Nrf2的转录激活。鉴于在自噬失调时Nrf2以p62依赖的方式持续激活，这种由Nrf2依赖的细胞保护基因反式激活的调节需要通过临床试验来验证。
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