IKKgamma serves as a docking subunit of the IkappaB kinase (IKK) and mediates interaction of IKK with the human T-cell leukemia virus Tax protein
- PMID: 10438454
- DOI: 10.1074/jbc.274.33.22911
IKKgamma serves as a docking subunit of the IkappaB kinase (IKK) and mediates interaction of IKK with the human T-cell leukemia virus Tax protein
Abstract
The tax gene product of human T-cell leukemia virus type I induces activation of transcription factor NF-kappaB, which contributes to deregulated expression of various cellular genes. Tax expression triggers persistent phosphorylation and degradation of the NF-kappaB inhibitory proteins IkappaBalpha and IkappaBbeta, resulting in constitutive nuclear expression of NF-kappaB. Recent studies demonstrate that Tax activates the IkappaB kinase (IKK), although the underlying mechanism remains unclear. In this report, we show that Tax physically interacts with a regulatory component of the IKK complex, the NF-kappaB essential modulator or IKKgamma (NEMO/IKKgamma). This molecular interaction appears to be important for recruiting Tax to the IKK catalytic subunits, IKKalpha and IKKbeta. Expression of NEMO/IKKgamma greatly promotes binding of Tax to IKKalpha and IKKbeta and stimulates Tax-mediated IKK activation. Interestingly, a mutant form of Tax defective in IKK activation exhibited a markedly diminished level of NEMO/IKKgamma association. These findings suggest that the physical interaction of Tax with NEMO/IKKgamma may play an important role in Tax-mediated IKK activation.
Similar articles
-
Activation of I-kappaB kinase by the HTLV type 1 Tax protein: mechanistic insights into the adaptor function of IKKgamma.AIDS Res Hum Retroviruses. 2000 Nov 1;16(16):1591-6. doi: 10.1089/08892220050193001. AIDS Res Hum Retroviruses. 2000. PMID: 11080796 Review.
-
Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein.Oncogene. 2000 Oct 26;19(45):5198-203. doi: 10.1038/sj.onc.1203894. Oncogene. 2000. PMID: 11064457
-
An alternative splice product of IkappaB kinase (IKKgamma), IKKgamma-delta, differentially mediates cytokine and human T-cell leukemia virus type 1 tax-induced NF-kappaB activation.J Virol. 2006 May;80(9):4227-41. doi: 10.1128/JVI.80.9.4227-4241.2006. J Virol. 2006. PMID: 16611882 Free PMC article.
-
IKKgamma mediates the interaction of cellular IkappaB kinases with the tax transforming protein of human T cell leukemia virus type 1.J Biol Chem. 1999 May 28;274(22):15297-300. doi: 10.1074/jbc.274.22.15297. J Biol Chem. 1999. PMID: 10336413
-
Regulation and function of IKK and IKK-related kinases.Sci STKE. 2006 Oct 17;2006(357):re13. doi: 10.1126/stke.3572006re13. Sci STKE. 2006. PMID: 17047224 Review.
Cited by
-
Mechanisms of Oncogenesis by HTLV-1 Tax.Pathogens. 2020 Jul 7;9(7):543. doi: 10.3390/pathogens9070543. Pathogens. 2020. PMID: 32645846 Free PMC article. Review.
-
Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity.Retrovirology. 2004 Aug 13;1:20. doi: 10.1186/1742-4690-1-20. Retrovirology. 2004. PMID: 15310405 Free PMC article. Review.
-
CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10494-9. doi: 10.1073/pnas.190245697. Proc Natl Acad Sci U S A. 2000. PMID: 10962033 Free PMC article.
-
Inhibition of methyltransferases results in induction of g2/m checkpoint and programmed cell death in human T-lymphotropic virus type 1-transformed cells.J Virol. 2008 Jan;82(1):49-59. doi: 10.1128/JVI.01497-07. Epub 2007 Oct 17. J Virol. 2008. PMID: 17942556 Free PMC article.
-
NF-kappaB and virus infection: who controls whom.EMBO J. 2003 Jun 2;22(11):2552-60. doi: 10.1093/emboj/cdg267. EMBO J. 2003. PMID: 12773372 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
