期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 367, 期 1, 页码 103-108出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.12.123
关键词
NEMO; disulfide bond; NF-kappa B; IKK; hydrogen peroxide; cysteine; molecular modeling
资金
- NCI NIH HHS [R01 CA047763, R01 CA047763-20, CA47763] Funding Source: Medline
- NIEHS NIH HHS [ES03775, R01 ES003775] Funding Source: Medline
NEMO is an essential regulatory component of the I kappa B kinase (IKK) complex, which controls activation of the NF-kappa B 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 (14202) 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 H2O2 decreases TNF alpha-induced IKK activity in NEMO-reconstituted cells, and that TNF alpha has a diminished ability to activate NF-kappa B 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. (C) 2007 Elsevier Inc. All rights reserved.
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