Dynamic redox control of NF-kappaB through glutaredoxin-regulated S-glutathionylation of inhibitory kappaB kinase beta.

ABSTRACT: The transcription factor NF-kappaB, a central regulator of immunity, is subject to regulation by redox changes. We now report that cysteine-179 of the inhibitory kappaB kinase (IKK) beta-subunit of the IKK signalosome is a central target for oxidative inactivation by means of S-glutathionylation. S-glutathionylation of IKK-beta Cys-179 is reversed by glutaredoxin (GRX), which restores kinase activity. Conversely, GRX1 knockdown sensitizes cells to oxidative inactivation of IKK-beta and dampens TNF-alpha-induced IKK and NF-kappaB activation. Primary tracheal epithelial cells from Glrx1-deficient mice display reduced NF-kappaB DNA binding, RelA nuclear translocation, and MIP-2 (macrophage inflammatory protein 2) and keratinocyte-derived chemokine production in response to LPS. Collectively,

SUBMITTER: Reynaert NL 

PROVIDER: S-EPMC1559757 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature