In vitro activation of the IκB kinase complex by human T-cell leukemia virus type-1 tax

Sohini Mukherjee, Veera S. Negi, Gladys Keitany, Yuetsu Tanaka, Kim Orth

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Human T-cell leukemia virus type-I expresses Tax, a 40-kDa oncoprotein that activates IκB kinase (IKK), resulting in constitutive activation of NFκB. Herein, we have developed an in vitro signaling assay to analyze IKK complex activation by recombinant Tax. Using this assay in combination with reporter assays, we demonstrate that Tax-mediated activation of IKK is independent of phosphatases. We show that sustained activation of the Tax-mediated activation of the NFκB pathway is dependent on an intact Hsp90-IKK complex. By acetylating and thereby preventing activation of the IKK complex by the Yersinia effector YopJ, we demonstrate that Tax-mediated activation of the IKK complex requires a phosphorylation step. Our characterization of an in vitro signaling assay system for the mechanism of Tax-mediated activation of the IKK complex with a variety of mutants and inhibitors results in a working model for the biochemical mechanism of Tax-induced activation.

Original languageEnglish (US)
Pages (from-to)15127-15133
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number22
DOIs
StatePublished - May 30 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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