Domain-specific interaction with the I kappa B kinase (IKK)regulatory subunit IKK gamma is an essential step in tax-mediated activation of IKK.
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 I kappa B kinase (IKK). Tax physically associates with the IKK regulatory subunit, IKK gamma, although the underlying biochemical mechanism and functional significance remain unclear. We show that the Tax-IKK gamma interaction requires two homologous leucine zipper domains located within IKK gamma. 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 IKK gamma binding. Interestingly, all the Tax mutants defective in IKK gamma binding failed to engage the IKK complex or stimulate IKK activity, and these functional defects can be rescued by fusing the Tax mutants to IKK gamma. These results provide mechanistic insights into how Tax specifically targets and functionally activates the cellular kinase IKK.
Xiao
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G
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Harhaj
E W
EW
Sun
S C
SC
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase; D007930:Leucine / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D016356:Gene Products, tax; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D007930:Leucine