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Biochem Biophys Res Commun. 2008 Feb 29;367(1):103-8. doi: 10.1016/j.bbrc.2007.12.123. Epub 2007 Dec 28.

Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347.

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  • 1Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.

Abstract

NEMO is an essential regulatory component of the IkappaB kinase (IKK) complex, which controls activation of the NF-kappaB signaling pathway. Herein, we show that NEMO exists as a disulfide-bonded dimer when isolated from several cell types and analyzed by SDS-polyacrylamide gel electrophoresis under non-reducing conditions. Treatment of cells with hydrogen peroxide (H(2)O(2)) induces further formation of NEMO dimers. Disulfide bond-mediated formation of NEMO dimers requires Cys54 and Cys347. The ability of these residues to form disulfide bonds is consistent with their location in a NEMO dimer structure that we generated by molecular modeling. We also show that pretreatment with H(2)O(2) decreases TNFalpha-induced IKK activity in NEMO-reconstituted cells, and that TNFalpha has a diminished ability to activate NF-kappaB DNA binding in cells reconstituted with NEMO mutant C54/347A. This study implicates NEMO as a target of redox regulation and presents the first structural model for the NEMO protein.

PMID:
18164680
[PubMed - indexed for MEDLINE]
PMCID:
PMC2277332
Free PMC Article

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