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Originally published In Press as doi:10.1074/jbc.M002970200 on July 20, 2000

J. Biol. Chem., Vol. 275, Issue 44, 34060-34067, November 3, 2000
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Domain-specific Interaction with the Ikappa B Kinase (IKK) Regulatory Subunit IKKgamma Is an Essential Step in Tax-mediated Activation of IKK*

Gutian XiaoDagger , Edward W. HarhajDagger , and Shao-Cong Sun§

From the Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

The human T-cell leukemia virus type 1 Tax oncoprotein deregulates the NF-kappa B signaling pathway by persistently stimulating a key signal transducer, the Ikappa B kinase (IKK). Tax physically associates with the IKK regulatory subunit, IKKgamma , although the underlying biochemical mechanism and functional significance remain unclear. We show that the Tax-IKKgamma interaction requires two homologous leucine zipper domains located within IKKgamma . These leucine zipper domains are unique for the presence of a conserved upstream region that is essential for Tax binding. Site-directed mutagenesis analysis revealed that a leucine-repeat region of Tax is important for IKKgamma binding. Interestingly, all the Tax mutants defective in IKKgamma binding failed to engage the IKK complex or stimulate IKK activity, and these functional defects can be rescued by fusing the Tax mutants to IKKgamma . These results provide mechanistic insights into how Tax specifically targets and functionally activates the cellular kinase IKK.

* This study was supported by Public Health Service Grant 1 R01 CA68471 (to S.-C.  S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Both authors contributed equally to this work.

§ To whom correspondence should be addressed: Dept. of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033. Tel.: 717-531-4164; Fax: 717-531-6522; E-mail: sxs70@psu.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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