Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome
Constitutive activation of the NF-κB pathway by the Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes. We have previously shown that Tax ubiquitylation on C-terminal lysines is critical for binding of Tax to IκB kinase (IKK) and its subsequ...
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Published in | Oncogene Vol. 27; no. 12; pp. 1665 - 1676 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
13.03.2008
Nature Publishing Nature Publishing Group Nature Publishing Group [1987-....] |
Subjects | |
Online Access | Get full text |
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Summary: | Constitutive activation of the NF-κB pathway by the Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes. We have previously shown that Tax ubiquitylation on C-terminal lysines is critical for binding of Tax to IκB kinase (IKK) and its subsequent activation. Here, we report that ubiquitylated Tax is not associated with active cytosolic IKK subunits, but binds endogenous IKK-α, -β, -γ, targeting them to the centrosome. K63-ubiquitylated Tax colocalizes at the centrosome with IKK-γ, while K48-ubiquitylated Tax is stabilized upon proteasome inhibition. Altogether, these results support a model in which K63-ubiquitylated Tax activates IKK in a centrosome-associated signalosome, leading to the production of Tax-free active cytoplasmic IKK. These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/sj.onc.1210804 |