IKKgamma serves as a docking subunit of the IkappaB kinase (IKK) and mediates interaction of IKK with the human T-cell leukemia virus Tax protein.
The tax gene product of human T-cell leukemia virus type I induces activation of transcription factor NF-kappaB, which contributes to deregulated expression of various cellular genes. Tax expression triggers persistent phosphorylation and degradation of the NF-kappaB inhibitory proteins IkappaBalpha and IkappaBbeta, resulting in constitutive nuclear expression of NF-kappaB. Recent studies demonstrate that Tax activates the IkappaB kinase (IKK), although the underlying mechanism remains unclear. In this report, we show that Tax physically interacts with a regulatory component of the IKK complex, the NF-kappaB essential modulator or IKKgamma (NEMO/IKKgamma). This molecular interaction appears to be important for recruiting Tax to the IKK catalytic subunits, IKKalpha and IKKbeta. Expression of NEMO/IKKgamma greatly promotes binding of Tax to IKKalpha and IKKbeta and stimulates Tax-mediated IKK activation. Interestingly, a mutant form of Tax defective in IKK activation exhibited a markedly diminished level of NEMO/IKKgamma association. These findings suggest that the physical interaction of Tax with NEMO/IKKgamma may play an important role in Tax-mediated IKK activation.
Harhaj
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EW
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Sun
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SC
D020134:Catalytic Domain; D004789:Enzyme Activation; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase; D009154:Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
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