Persistent activation of nf-κb by the tax transforming protein of htlv-1: hijacking cellular iκb kinases

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

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FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PRIMARY CELLS FROM PATIENTS WITH ADULT T CELL LEUKEMIA/LYMPHOMA DEPEND ON HTLV-1 TAX EXPRESSION FOR NF-ΚB ACTIVATION

AND SURVIVAL Article Open access 03 May 2023 ADAP1 PROMOTES LATENT HIV-1 REACTIVATION BY SELECTIVELY TUNING KRAS–ERK–AP-1 T CELL SIGNALING-TRANSCRIPTIONAL AXIS Article Open access 01 March

2022 THE TYROSINE KINASE KDR IS ESSENTIAL FOR THE SURVIVAL OF HTLV-1-INFECTED T CELLS BY STABILIZING THE TAX ONCOPROTEIN Article Open access 25 June 2024 REFERENCES * Akagi T, Ono H, Nyunoya

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* Zhao LJ and Giam CZ. . 1992 _Proc. Natl. Acad. Sci. USA_ 89: 7070–7474. * Zhao Q and Lee FS. . 1999 _J. Biol. Chem._ 274: 8355–8358. Download references ACKNOWLEDGEMENTS We thank Tom

Maniatis for helpful comments and apologize to those colleagues whose published data could not be cited due to space limitations. Research performed in the authors' laboratories on the

subject under review was supported by RO1 grants CA68471 (to S-C Sun) and CA82556 (to DW Ballard) from the National Institutes of Health and by the Howard Hughes Medical Institute. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, 17033, Pennsylvania, PA,

USA Shao-Cong Sun * Department of Microbiology and Immunology, Vanderbilt University School of Medicine, 802 Light Hall, Nashville, 37232-0295, Tennessee, TN, USA Dean W Ballard Authors *

Shao-Cong Sun View author publications You can also search for this author inPubMed Google Scholar * Dean W Ballard View author publications You can also search for this author inPubMed 

Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sun, SC., Ballard, D. Persistent activation of NF-κB by the Tax transforming protein of

HTLV-1: hijacking cellular IκB kinases. _Oncogene_ 18, 6948–6958 (1999). https://doi.org/10.1038/sj.onc.1203220 Download citation * Published: 22 November 1999 * Issue Date: 22 November 1999

* DOI: https://doi.org/10.1038/sj.onc.1203220 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is

not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * HTLV-1 * Tax * NF-κB * IκB * IKK * viral

oncogenesis, leukemia