Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit.

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Jeon KI, Byun MS, Jue DM

Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit.

Exp Mol Med. 2003 Apr 30;35(2):61-6.

PubMed ID

12754408 [ View in PubMed

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Abstract

Antirheumatic gold compounds have been shown to inhibit NF-kappaB activation by blocking IkappaB kinase (IKK) activity. To examine the possible inhibitory mechanism of gold compounds, we expressed wild type and mutant forms of IKKalpha and beta subunits in COS-7 cells and determined the effect of gold on the activity of these enzymes both in vivo and in vitro. Substitution of Cys-179 of IKKbeta with alanine (C179A) rendered the enzyme to become resistant to inhibition by a gold compound auranofin, however, similar protective effect was not observed with an equivalent level of IKKalpha (C178A) mutant expressed in the cells. Auranofin inhibited constitutively active IKKalpha and beta and variants; IKKalpha (S176E, S180E) or IKKbeta (S177E, S181E), suggesting that gold directly cause inhibition of activated enzyme. The different inhibitory effect of auranofin on IKKalpha (C178A) and IKKbeta (C179A) mutants indicates that gold could inhibit the two subunits of IKK in a different mode, and the inhibition of NF-kappaB and IKK activation induced by inflammatory signals in gold-treated cells appears through its interaction with Cys-179 of IKKbeta.

DrugBank Data that Cites this Article

Drugs

Auranofin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Auranofin	Inhibitor of nuclear factor kappa-B kinase subunit beta	Protein	Humans	Yes	Inhibitor	Details