细胞质
功能(生物学)
细胞生物学
KEAP1型
化学
物理
生物
生物化学
转录因子
基因
作者
Laurie M. Zipper,R. Timothy Mulcahy
标识
DOI:10.1074/jbc.m206530200
摘要
Transactivation of phase II detoxification enzymes and antioxidant proteins is mediated by the Cap'N′Collar transcription factor, Nrf2, which is sequestered in the cytoplasm by the actin-binding protein Keap1. Mutation of a conserved serine (S104A) within the Keap1 BTB/POZ domain disrupts Keap1 dimerization and eliminates the ability of Keap1 to sequester Nrf2 in the cytoplasm and repress Nrf2 transactivation. Disruption of endogenous Keap1 dimerization using BTB/POZ dominant negative proteins also inhibits the ability of Keap1 to retain Nrf2 in the cytoplasm. Exposure to an electrophilic agent that induces Nrf2 release and nuclear translocation disrupts formation of a Keap1 complex in vivo. Collectively, these data support the conclusion that Keap1 dimerization is required for Nrf2 sequestration and transcriptional repression. Furthermore, exposure to inducing agents disrupts the Keap1 dimerization function and results in Nrf2 release.
科研通智能强力驱动
Strongly Powered by AbleSci AI