Format

Send to

Choose Destination
Chem Biol. 2010 May 28;17(5):537-47. doi: 10.1016/j.chembiol.2010.03.013.

A small-molecule inducer of the antioxidant response element.

Author information

1
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

Eukaryotic cells counteract oxidative and other environmental stress through the activation of Nrf2, the transcription factor that controls the expression of a host of protective enzymes by binding to the antioxidant response element (ARE). The electrophilic molecules that are able to activate Nrf2 and its downstream target genes have demonstrated therapeutic potential in carcinogen-induced tumor models. Using a high-throughput cellular screen, we discovered a class of ARE activator, which we named AI-1, that activates Nrf2 by covalently modifying Keap1, the negative regulator of Nrf2. Biochemical studies indicated that modification of Cys151 of Keap1 by AI-1 disrupted the ability of Keap1 to serve as an adaptor for Cul3-Keap1 ubiquitin ligase complex, thereby causing stabilization and transcriptional activation of Nrf2. AI-1 and its biotinylated derivative are useful pharmacological probes for investigating the molecular details of the cellular antioxidant response.

PMID:
20534351
DOI:
10.1016/j.chembiol.2010.03.013
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center