Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome

作者：Kfoury Y; Nasr R; Favre Bonvin A; El Sabban M; Renault N; Giron M L; Setterblad N; El Hajj H; Chiari E; Mikati A G; Hermine O; Saib A; de The H; Pique C; Bazarbachi A^*

来源：Oncogene, 2008, 27(12): 1665-1676.

DOI：10.1038/sj.onc.1210804

• 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.

• 出版日期2008-3-13