Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Keap1 is a highly redox-sensitive member of the BTB-Kelch family that assembles with the Cul3 protein to form a Cullin-RING E3 ligase complex for the degradation of Nrf2. Oxidative stress disables Keap1, allowing Nrf2 protein levels to accumulate for the transactivation of critical stress response genes. Consequently, the Keap1-Nrf2 system is extensively pursued for the development of protein-protein interaction inhibitors that will stabilize Nrf2 for therapeutic effect in conditions of neurodegeneration, inflammation, and cancer. Here we review current progress toward the structure determination of Keap1 and its protein complexes with Cul3, Nrf2 substrate, and small-molecule antagonists. Together the available structures establish a rational three-dimensional model to explain the two-site binding of Nrf2 as well as its efficient ubiquitination.

Original publication

DOI

10.1016/j.freeradbiomed.2015.05.034

Type

Journal article

Journal

Free Radic Biol Med

Publication Date

11/2015

Volume

88

Pages

101 - 107

Keywords

BTB, Cullin, Free radicals, Keap1, Kelch, Nrf2, Ubiquitin, Animals, Humans, Intracellular Signaling Peptides and Proteins, Models, Molecular, NF-E2-Related Factor 2, Oxidative Stress, Signal Transduction