Activation of SKN-1 by novel kinases in Caenorhabditis elegans.
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.
Kell
Alison
A
Institute for Behavioral Genetics, University of Colorado at Boulder, Box 447, Boulder, CO 80309, USA.
Ventura
Natascia
N
Kahn
Nate
N
Johnson
Thomas E
TE
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000378:metabolism; D008136:Longevity; D018384:Oxidative Stress; D010770:Phosphotransferases / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; D010770:Phosphotransferases; D051550:I-kappa B Kinase