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

Research output: Contribution to journalArticle

225 Citations (Scopus)

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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Taxation
Phosphotransferases
Chemical activation
Phosphorylation
MAP Kinase Kinase Kinase 1
tax Gene Products
Human T-lymphotropic virus 1
Cellular Immunity
Serine
Human T-lymphotrophic virus 1 tax protein
Degradation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Yin, M. J., Christerson, L. B., Yamamoto, Y., Kwak, Y. T., Xu, S., Mercurio, F., ... 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

HTLV-I tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation. / Yin, Min Jean; Christerson, Lori B.; Yamamoto, Yumi; Kwak, Youn Tae; Xu, Shuichan; Mercurio, Frank; Barbosa, Miguel; Cobb, Melanie H.; Gaynor, Richard B.

In: Cell, Vol. 93, No. 5, 29.05.1998, p. 875-884.

Research output: Contribution to journalArticle

Yin, MJ, Christerson, LB, Yamamoto, Y, Kwak, YT, Xu, S, Mercurio, F, Barbosa, M, Cobb, MH & Gaynor, RB 1998, 'HTLV-I tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation', Cell, vol. 93, no. 5, pp. 875-884. https://doi.org/10.1016/S0092-8674(00)81447-6
Yin MJ, Christerson LB, Yamamoto Y, Kwak YT, Xu S, Mercurio F et al. HTLV-I tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation. Cell. 1998 May 29;93(5):875-884. https://doi.org/10.1016/S0092-8674(00)81447-6
Yin, Min Jean ; Christerson, Lori B. ; Yamamoto, Yumi ; Kwak, Youn Tae ; Xu, Shuichan ; Mercurio, Frank ; Barbosa, Miguel ; Cobb, Melanie H. ; Gaynor, Richard B. / HTLV-I tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation. In: Cell. 1998 ; Vol. 93, No. 5. pp. 875-884.
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