期刊
ONCOGENE
卷 27, 期 12, 页码 1665-1676出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210804
关键词
NF-kappa B; I kappa B kinase; centrosome; HTLV-I; Tax; ubiquitin
Constitutive activation of the NF-kappa B 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 I kappa B kinase (IKK) and its subsequent activation. Here, we report that ubiquitylated Tax is not associated with active cytosolic IKK subunits, but binds endogenous IKK-alpha, -beta, -gamma, targeting them to the centrosome. K63-ubiquitylated Tax colocalizes at the centrosome with IKK-gamma, 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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