Send to

Choose Destination
Free Radic Biol Med. 2007 Dec 1;43(11):1560-6. Epub 2007 Sep 7.

Activation of SKN-1 by novel kinases in Caenorhabditis elegans.

Author information

Institute for Behavioral Genetics, University of Colorado at Boulder, Box 447, Boulder, CO 80309, USA.


Here we use a large-scale RNAi suppression screen to identify additional kinases playing a role in the activation of SKN-1 in response to oxidative stress. The SKN-1 transcription factor specifies cell fate of the EMS blastomere at the four-cell stage in the nematode Caenorhabditis elegans and also directs transcription of many genes responding to oxidative stress, including glutathione S-transferase, NAD(P)H:quinone oxidoreductase, and superoxide dismutase. SKN-1 localizes to the nucleus and directs transcription following exposure to paraquat, heat, hyperbaric oxygen, and sodium azide. Previous studies have identified GSK-3 as an inhibitor of SKN-1 nuclear localization, in the absence of stress, and PMK-1 as an activator of SKN-1 during periods of oxidative stress. Through this screen we have identified four kinases, MKK-4, IKK epsilon-1, NEKL-2, and PDHK-2, which are necessary for the nuclear localization of SKN-1 in response to oxidative stress. Inhibition of two of these kinases results in shorter life span and increased sensitivity to stress.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center