NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I tax-mediated NF-κB activation

Mark Uhlik, Li Feng Good, Gutian Xiao, Edward W. Harhaj, Ebrahim Zandi, Michael Karin, Shao Cong Sun

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

The tax gene product of human T-cell leukemia virus I induces aberrant expression of various cellular genes, which contributes to transformation of host cells. Induction of many Tax target genes is mediated through transcription factor NF-κB. Here we show that Tax triggers activation of cellular protein kinases, IκB kinase α (IKKα) and IKKβ, which phosphorylate the NF-κB inhibitory protein IκBα, resulting in its degradation and NF-κB activation. Constitutive IKK activation occurs in both Tax-transfected and human T-cell leukemia virus I-infected T cells. We further demonstrate that Tax-mediated NF-κB signaling also requires the NF- κB-inducing kinase (NIK). Consistently, inactive forms of either IKKs or NIK attenuate Tax-mediated NF-κB activation. Therefore, Tax activates NF-κB by targeting cellular signaling molecules, including both IKKs and NIK.

Original languageEnglish (US)
Pages (from-to)21132-21136
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number33
DOIs
StatePublished - Aug 14 1998

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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