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Persistent activation of NF-κB by the Tax transforming protein of HTLV-1: hijacking cellular IκB kinases

Persistent activation of NF-κB by the Tax transforming protein of HTLV-1: hijacking cellular IκB... Biochemical coupling of transcription factor NF-κB to antigen and co-stimulatory receptors is required for the temporal control of T-cell proliferation. In contrast to its transitory activation during normal growth-signal transduction, NF-κB is constitutively deployed in T-cells transformed by the type 1 human T-cell leukemia virus (HTLV-1). This viral/host interaction is mediated by the HTLV-1-encoded Tax protein, which has potent oncogenic properties. As reviewed here, Tax activates NF-κB primarily via a pathway leading to the chronic phosphorylation and degradation of IκBα, a cytoplasmic inhibitor of NF-κB. To access this pathway, Tax associates stably with a cytokine-inducible IκB kinase (IKK), which contains both catalytic (IKKα and IKKβ) and noncatalytic (IKKγ) subunits. Unlike their transiently induced counterparts in cytokine-treated cells, Tax-associated forms of IKKα and IKKβ are persistently activated in HTLV-1-infected T cells. Acquisition of the deregulated IKK phenotype is contingent on the presence of IKKγ, which functions as a molecular adaptor in the assembly of pathologic Tax/IκB kinase complexes. These findings highlight a key mechanistic role for IKK in the Tax/NF-κB signaling axis and define new intracellular targets for the therapeutic control of HTLV-1-associated disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Oncogene Springer Journals

Persistent activation of NF-κB by the Tax transforming protein of HTLV-1: hijacking cellular IκB kinases

Sun, Shao-Cong; Ballard, Dean W
Oncogene , Volume 18 (49) – Nov 22, 1999
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References (171)

Publisher
Springer Journals
Copyright
Copyright © 1999 by Macmillan Publishers Limited
Subject
Medicine & Public Health; Medicine/Public Health, general; Internal Medicine; Cell Biology; Human Genetics; Oncology; Apoptosis
ISSN
0950-9232
eISSN
1476-5594
DOI
10.1038/sj.onc.1203220
Publisher site
See Article on Publisher Site

Abstract

Biochemical coupling of transcription factor NF-κB to antigen and co-stimulatory receptors is required for the temporal control of T-cell proliferation. In contrast to its transitory activation during normal growth-signal transduction, NF-κB is constitutively deployed in T-cells transformed by the type 1 human T-cell leukemia virus (HTLV-1). This viral/host interaction is mediated by the HTLV-1-encoded Tax protein, which has potent oncogenic properties. As reviewed here, Tax activates NF-κB primarily via a pathway leading to the chronic phosphorylation and degradation of IκBα, a cytoplasmic inhibitor of NF-κB. To access this pathway, Tax associates stably with a cytokine-inducible IκB kinase (IKK), which contains both catalytic (IKKα and IKKβ) and noncatalytic (IKKγ) subunits. Unlike their transiently induced counterparts in cytokine-treated cells, Tax-associated forms of IKKα and IKKβ are persistently activated in HTLV-1-infected T cells. Acquisition of the deregulated IKK phenotype is contingent on the presence of IKKγ, which functions as a molecular adaptor in the assembly of pathologic Tax/IκB kinase complexes. These findings highlight a key mechanistic role for IKK in the Tax/NF-κB signaling axis and define new intracellular targets for the therapeutic control of HTLV-1-associated disease.

Journal

Oncogene – Springer Journals

Published: Nov 22, 1999

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