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PNAS 97 (19): 10489-10493

Copyright © 2000 by the National Academy of Sciences.


Act1, an NF-{kappa}B-activating protein

Xiaoxia Li*, Mairead Commane{dagger}, Huiqin Nie*, Xianxin Hua{ddagger}, Moitreyee Chatterjee-Kishore{dagger}, David Wald{dagger}, Michael Haag{dagger}, and George R. Stark{dagger},§

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

Contributed by George R. Stark

Accepted for publication June 8, 2000.

Abstract: 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 I{kappa}B kinase (IKK), leading to the liberation of NF-{kappa}B from its complex with I{kappa}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}

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF274303).

Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.160265197.

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