Domain-specific interaction with the IκB kinase (IKK) regulatory subunit IKKγ is an essential step in tax-mediated activation of IKK

Gutian Xiao, Edward Harhaj, Shao Cong Sun

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

The human T-cell leukemia virus type 1 Tax oncoprotein deregulates the NF-κB signaling pathway by persistently stimulating a key signal transducer, the IκB kinase (IKK). Tax physically associates with the IKK regulatory subunit, IKKγ, although the underlying biochemical mechanism and functional significance remain unclear. We show that the Tax-IKKγ interaction requires two homologous leucine zipper domains located within IKKγ. 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 IKKγ binding. Interestingly, all the Tax mutants defective in IKKγ binding failed to engage the IKKγ complex or stimulate IKK activity, and these functional defects can be rescued by fusing the Tax mutants to IKKγ. These results provide mechanistic insights into how Tax specifically targets and functionally activates the cellular kinase IKK.

Original languageEnglish (US)
Pages (from-to)34060-34067
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number44
DOIs
StatePublished - Nov 3 2000

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Leucine Zippers
Taxation
Phosphotransferases
Chemical activation
Deltaretrovirus
Oncogene Proteins
Site-Directed Mutagenesis
Transducers
Leucine
Mutagenesis
T-cells
Viruses
Defects

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Domain-specific interaction with the IκB kinase (IKK) regulatory subunit IKKγ is an essential step in tax-mediated activation of IKK",
abstract = "The human T-cell leukemia virus type 1 Tax oncoprotein deregulates the NF-κB signaling pathway by persistently stimulating a key signal transducer, the IκB kinase (IKK). Tax physically associates with the IKK regulatory subunit, IKKγ, although the underlying biochemical mechanism and functional significance remain unclear. We show that the Tax-IKKγ interaction requires two homologous leucine zipper domains located within IKKγ. 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 IKKγ binding. Interestingly, all the Tax mutants defective in IKKγ binding failed to engage the IKKγ complex or stimulate IKK activity, and these functional defects can be rescued by fusing the Tax mutants to IKKγ. These results provide mechanistic insights into how Tax specifically targets and functionally activates the cellular kinase IKK.",
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Domain-specific interaction with the IκB kinase (IKK) regulatory subunit IKKγ is an essential step in tax-mediated activation of IKK. / Xiao, Gutian; Harhaj, Edward; Sun, Shao Cong.

In: Journal of Biological Chemistry, Vol. 275, No. 44, 03.11.2000, p. 34060-34067.

Research output: Contribution to journalArticle

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