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Fig. 2 | Cell Communication and Signaling

Fig. 2

From: Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review

Fig. 2

Schematic structures of Keap1 and Nrf2. a Nrf2 comprises seven Nrf2-ECH homology (Neh) domains, Neh1-Neh7. Among these domains, Neh2 and Neh6 are important for binding with the negative regulators Keap1 and β-TrCP, respectively, consequently causing Nrf2 ubiquitination and degradation. Neh1 contains a cap ‘n’ collar (CNC) basic-region leucine zipper (bZIP) domain that is important for interacting with small MAF (sMAF) proteins and DNA. Neh1 also holds a nuclear localization signal (NLS) which is required for the nuclear translocation of Nrf2. Neh3, Neh4, and Neh5 domains are necessary for transactivation. Neh7 is important for binding with an Nrf2 repressor, the retinoic X receptor α (RXRα). b Keap1 comprises an N-terminal region (NTR), a broad complex, Tramtrack and Bric-à-Brac (BTB) domain, an intervening region (IVR), six Kelch repeats, and a C-terminal region (CTR). Among these domains, BTB domain is responsible for the homodimerization of Keap1 and the binding with Cullin3 (Cul3) E3 ligase. BTB also harbors cysteine residues, which are reactive to electrophiles and reactive oxygen species (ROS). Kelch repeats contain binding sites that are important for interacting with Nrf2, p62, and other E/STGE proteins. IVR contains a nuclear export signal (NES), which regulates the cytoplasmic localization of Keap1

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