Oxidative and Electrophilic Stresses Activate Nrf2 through Inhibition of Ubiquitination Activity of Keap1

• DOI: 10.1128/mcb.26.1.221-229.2006
• Publication Date: 2005-12-14T06:08:44Z
• Authors: Akira Kobayashi; Moon-Il Kang; Yoriko Watai; Kit I. Tong; Takahiro Shibata; Koji Uchida; Masayuki Yamamoto
• Keywords: KEAP1

The Keap1-Nrf2 system is the major regulatory pathway of cytoprotective gene expression against oxidative and/or electrophilic stresses. Keap1 acts as a stress sensor protein in this system. While constitutively suppresses Nrf2 activity under unstressed conditions, oxidants or electrophiles provoke repression activity, inducing activation. However, precise molecular mechanisms behind liberation from presence remain to be elucidated. We hypothesized that and stresses induce nuclear accumulation by affecting Keap1-mediated rapid turnover Nrf2, since such was diminished synthesis inhibitor cycloheximide. both Cys273 Cys288 residues are required for suppressing accumulation, treatment cells with mutation these cysteine alanine did not affect association either vivo vitro. Rather, treatments impaired proteasomal degradation Nrf2. These results support contention synthesized de novo after exposure accumulates nucleus bypassing gate sensory mechanism closely linked