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First published online May 26, 2006
Journal of Experimental Biology 209, 2337-2343 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02209
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Plasticity in cell defence: access to and reactivity of critical protein residues and DNA response elements

Chris Goldring1,*, Neil Kitteringham1, Rosalind Jenkins1, Ian Copple1, Jean-Francois Jeannin2 and B. Kevin Park1

1 Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L69 3GE, Merseyside, UK
2 Cancer Immunotherapy Laboratory, Ecole Pratique des Hautes Etudes, INSERM U517, Faculty of Medicine, Dijon, France


Figure 1
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  		Fig. 1. Cellular response to stress.

 

Figure 2
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  		Fig. 2. In vivo footprinting of gene promoters. See text for details.

 

Figure 3
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  		Fig. 3. NF-kappa B occupation may contribute to tolerance.

 

Figure 4
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  		Fig. 4. Role of the Keap1-Nrf2-ARE system in the regulation of the antioxidant response. Sensing of chemical stress by Keap1 switches the fate of Nrf2 from proteasomal degradation to nuclear translocation, where it activates multiple genes involved in cellular defence.

 

Figure 5
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  		Fig. 5. Schematic representation of Keap1, indicating the relative cysteine content of the various regions.

 

Figure 6
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  		Fig. 6. Model of the activation of Nrf2 through release from the Keap1 dimer induced by oxidation (S–S) or arylation (X) of cysteine thiols 273 and 288 [adapted from (Wakabayashi, 2004)]. See text for further explanation.

 

Figure 7
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  		Fig. 7. Nrf2 nuclear translocation is related to the administered dose of paracetamol. Mice were treated with the indicated doses of paracetamol. After 1 h they were sacrificed, livers were removed, nuclei prepared and nuclear proteins extracted. These were separated using SDS–PAGE, alongside a recombinant mouse Nrf2 positive control, transferred to a nitrocellulose membrane, probed for Nrf2 using a polyclonal anti-Nrf2 antiserum and visualised using chemiluminescence. Each data point in the blot and in the response-curve is obtained from pooled extracts of five animals (+ s.d.).

 

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© The Company of Biologists Ltd 2006