Authors
Keiko Taguchi, Nanako Fujikawa, Masaaki Komatsu, Tetsuro Ishii, Michiaki Unno, Takaaki Akaike, Hozumi Motohashi, Masayuki Yamamoto
Publication date
2012/8/21
Journal
Proceedings of the National Academy of Sciences
Volume
109
Issue
34
Pages
13561-13566
Publisher
National Academy of Sciences
Description
The Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system is essential for cytoprotection against oxidative and electrophilic insults. Under unstressed conditions, Keap1 serves as an adaptor for ubiquitin E3 ligase and promotes proteasomal degradation of Nrf2, but Nrf2 is stabilized when Keap1 is inactivated under oxidative/electrophilic stress conditions. Autophagy-deficient mice show aberrant accumulation of p62, a multifunctional scaffold protein, and develop severe liver damage. The p62 accumulation disrupts the Keap1-Nrf2 association and provokes Nrf2 stabilization and accumulation. However, individual contributions of p62 and Nrf2 to the autophagy-deficiency–driven liver pathogenesis have not been clarified. To examine whether Nrf2 caused the liver injury independent of p62, we crossed liver-specific Atg7::Keap1-Alb double-mutant mice into p62- and Nrf2-null backgrounds …
Scholar articles
K Taguchi, N Fujikawa, M Komatsu, T Ishii, M Unno… - Proceedings of the National Academy of Sciences, 2012