HTLV-I tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation

Min Jean Yin, Lori B. Christerson, Yumi Yamamoto, Youn Tae Kwak, Shuichan Xu, Frank Mercurio, Miguel Barbosa, Melanie H. Cobb, Richard B. Gaynor

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Abstract

NF-κB, a key regulator of the cellular inflammatory and immune response, is activated by the HTLV-I transforming and transactivating protein Tax. We show that Tax binds to the amino terminus of the protein kinase MEKK1, a component of an IκB kinase complex, and stimulates MEKK1 kinase activity. Tax expression increases the activity of IκB kinase β (IKKβ) to enhance phosphorylation of serine residues in IκBα that lead to its degradation. Dominant negative mutants of both IKKβ and MEKK1 prevent Tax activation of the NF-κB pathway. Furthermore, recombinant MEKK1 stimulates IKKβ phosphorylation of IκBα. Thus, Tax-mediated increases in NF-κB nuclear translocation result from direct interactions of Tax and MEKK1 leading to enhanced IKKβ phosphorylation of IκBα.

Original languageEnglish (US)
Pages (from-to)875-884
Number of pages10
JournalCell
Volume93
Issue number5
DOIs
StatePublished - May 29 1998

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yin, M. J., Christerson, L. B., Yamamoto, Y., Kwak, Y. T., Xu, S., Mercurio, F., Barbosa, M., Cobb, M. H., & Gaynor, R. B. (1998). HTLV-I tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation. Cell, 93(5), 875-884. https://doi.org/10.1016/S0092-8674(00)81447-6