IKKgamma mediates the interaction of cellular IkappaB kinases with the tax transforming protein of human T cell leukemia virus type 1.
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.
Chu
Z L
ZL
Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0295, USA.
Shin
Y A
YA
Yang
J M
JM
DiDonato
J A
JA
Ballard
D W
DW
D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase; D019169:Jurkat Cells; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
D016356:Gene Products, tax; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human