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Toxicological Sciences vol. 83 no. 1 © Society of Toxicology 2005; all rights reserved.
TOXICOLOGICAL HIGHLIGHT |
Compartmentalization of Redox Regulation of Cell Responses
Center for Developmental Pharmacology and Toxicology, Columbus Children's Research Institute, 700 Children's Drive, Columbus, Ohio 43205
1 For correspondence via fax: (614) 722-2774. E-mail: smithcv@chi.osu.edu
Received November 11, 2004; accepted November 11, 2004
| The first 10% of the full text of this article appears below. |
In the November issue of Toxicological Sciences, Hansen et al. (2004)
report results that they conclude show that a transcriptional regulator, NE-F2-related factor 2 (Nrf-2), exhibits compartmentally differential redox responses. The working model put forward by Hansen is conceptually straightforward. In the model, Nrf-2 is retained in the cytosol by Keap-1, but when critical thiols on Keap-1 are oxidized, Nrf-2 is released and translocated to the nucleus, where Nrf-2 participates in the transcriptional activation of numerous genes. For Nrf-2 to be fully functional in transcriptional activation, a key cysteine residue must be in the thiol (reduced) form. The model proposed by Hansen et al. overlooks the contributions of phosphorylation in activation of Nrf-2 (Huang et al., 2002; Nguyen et al., 2004) and
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