Dietary ITCs (isothiocyanates) prevent cancer and show other bioactivities in vivo. As electrophiles, ITCs may covalently modify cellular proteins. Using a novel proteomics screen, we identified MIF (macrophage migration inhibitory factor) as the principal target of nutrient ITCs in intact cells. ITCs covalently modify the N-terminal proline residue of MIF and extinguish its catalytic tautomerase activity. MIF deficiency does not prevent induction of Phase 2 gene expression, a hallmark of many cancer chemopreventives, including ITCs. Due to the emerging role of MIF in the control of malignant cell growth and its clear involvement in inflammation, inhibition of MIF by nutrient ITCs suggests therapeutic strategies for inflammatory diseases and cancer.
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November 2009
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Research Article|
October 12 2009
Nutrient isothiocyanates covalently modify and inhibit the inflammatory cytokine macrophage migration inhibitory factor (MIF)
Janet V. Cross;
Janet V. Cross
1
*Department of Pathology, University of Virginia, Charlottesville, VA 22908, U.S.A.
1To whom correspondence should be addressed (email cross@virginia.edu).
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Joshua M. Rady;
Joshua M. Rady
*Department of Pathology, University of Virginia, Charlottesville, VA 22908, U.S.A.
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Frank W. Foss, Jr;
Frank W. Foss, Jr
2
†Department of Chemistry, University of Virginia, Charlottesville, VA 22908, U.S.A.
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Charles E. Lyons;
Charles E. Lyons
*Department of Pathology, University of Virginia, Charlottesville, VA 22908, U.S.A.
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Timothy L. Macdonald;
Timothy L. Macdonald
†Department of Chemistry, University of Virginia, Charlottesville, VA 22908, U.S.A.
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Dennis J. Templeton
Dennis J. Templeton
*Department of Pathology, University of Virginia, Charlottesville, VA 22908, U.S.A.
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Biochem J (2009) 423 (3): 315–321.
Article history
Received:
July 30 2009
Revision Received:
August 20 2009
Accepted:
September 01 2009
Accepted Manuscript online:
September 01 2009
Citation
Janet V. Cross, Joshua M. Rady, Frank W. Foss, Charles E. Lyons, Timothy L. Macdonald, Dennis J. Templeton; Nutrient isothiocyanates covalently modify and inhibit the inflammatory cytokine macrophage migration inhibitory factor (MIF). Biochem J 1 November 2009; 423 (3): 315–321. doi: https://doi.org/10.1042/BJ20091170
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