Research ResourceImmunology

Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells

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Science Signaling  13 Sep 2016:
Vol. 9, Issue 445, pp. rs10
DOI: 10.1126/scisignal.aaf7694

Uncovering how a drug works

The drug dimethyl fumarate (DMF), which is used to treat autoimmune diseases, including psoriasis and multiple sclerosis, may act by modifying cysteine residues in proteins. A better understanding of its mechanism of action and target proteins is required because it can cause life-threatening infections in some patients. Blewett et al. used a chemical proteomics approach to identify cysteine residues in human T cell proteins that reacted with DMF. One such target, the kinase PKCθ, contains two cysteine residues that were targeted by DMF, which prevented PKCθ from interacting with the T cell costimulatory receptor CD28 and mediating full T cell activation. This approach should aid in developing similar drugs with fewer side effects.

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