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First published online 20 October 2009
doi: 10.1242/jcs.054007

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HSCARG inhibits activation of NF-B by interacting with IB kinase-β

National Laboratory of Protein Engineering and Plant Genetic Engineering, Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871, China

^* Author for correspondence (xiaofengz{at}pku.edu.cn)

Accepted 17 August 2009

HSCARG is a recently identified human NADPH sensor. Our previous studies have shown that HSCARG can affect NO production and cell viability, but the signal pathway mediated by this protein is unknown. Here, we show that HSCARG is involved in the NF-B signaling pathway and find that HSCARG suppresses TNF- and IL1-induced NF-B activation in a dose-dependent manner. Co-immunoprecipitation and immunofluorescence analyses demonstrate that HSCARG interacts and colocalizes with IKKβ. HSCARG inhibits the phosphorylation of IKKβ and further blocks the degradation of IB, the substrate of IKKβ, which retains NF-B in the cytoplasm and suppresses its activity. In addition, our data indicate that IKKβ is required for HSCARG-inhibited NF-B activation. Our findings delineate a pathway by which HSCARG negatively regulates NF-B activation.

Key words: HSCARG, NF-B, IKKβ, phosphorylation

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