IKKγ Mediates the Interaction of Cellular IκB Kinases with the Tax Transforming Protein of Human T Cell Leukemia Virus Type 1
Autor: | Young Ah Shin, Joseph A. DiDonato, Dean W. Ballard, Zhi Liang Chu, Jin Ming Yang |
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Rok vydání: | 1999 |
Předmět: |
Kinase
Protein subunit Signal transducing adaptor protein Gene Products tax Cell Biology IκB kinase Protein Serine-Threonine Kinases Biology Biochemistry Virology I-kappa B Kinase Cell biology Jurkat Cells IκBα Gene Expression Regulation Cytoplasm Mutation Humans Phosphorylation Molecular Biology Transcription factor health care economics and organizations Protein Binding Sequence Deletion |
Zdroj: | Journal of Biological Chemistry. 274:15297-15300 |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.274.22.15297 |
Popis: | The Tax oncoprotein of human T cell leukemia virus type 1 constitutively activates transcription factor NF-kappaB by a mechanism involving Tax-induced phosphorylation of IkappaBalpha, a labile cytoplasmic inhibitor of NF-kappaB. To trigger this signaling cascade, Tax associates stably with and persistently activates a cellular IkappaB kinase (IKK) containing both catalytic (IKKalpha and IKKbeta) and noncatalytic (IKKgamma) subunits. We now demonstrate that IKKgamma enables Tax to dock with the IKKbeta catalytic subunit, resulting in chronic IkappaB kinase activation. Mutations in either IKKgamma or Tax that prevent formation of these higher order Tax.IKK complexes also interfere with the ability of Tax to induce IKKbeta catalytic function in vivo. Deletion mapping studies indicate that amino acids 1-100 of IKKgamma are required for this Tax targeting function. Together, these findings identify IKKgamma as an adaptor protein that directs the stable formation of pathologic Tax.IKK complexes in virally infected T cells. |
Databáze: | OpenAIRE |
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