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PNAS 97 (19): 10489-10493

Copyright © 2000 by the National Academy of Sciences.

Genetics
 Act1, an NF-kappa B-activating protein

Xiaoxia Li*, Mairead Commanedagger , Huiqin Nie*, Xianxin HuaDagger , Moitreyee Chatterjee-Kishoredagger , David Walddagger , Michael Haagdagger , and George R. Starkdagger ,§

Departments of * Immunology and dagger  Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195; and Dagger  Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142

Contributed by George R. Stark, June 8, 2000

Use of an NF-kappa B-dependent selectable marker facilitated the isolation of a cell line containing a cDNA encoding Act1, an NF-kappa B activator. Act1 associates with and activates Ikappa B kinase (IKK), leading to the liberation of NF-kappa B from its complex with Ikappa B. Many signaling pathways that liberate NF-kappa B also activate activating transcription factor (ATF) and activator protein 1 (AP-1) through Jun kinase (JNK). Act1 also activates JNK, suggesting that it might be part of a multifunctional complex involved in the activation of both NF-kappa B and JNK. Act1 fails to activate NF-kappa B in an IL-1-unresponsive mutant cell line in which all known signaling components are present, suggesting that it interacts with an unknown component in IL-1 signaling.

§ To whom reprint requests should be addressed. E-mail: starkg{at}ccf.org.

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