Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome

• Published in: Oncogene Vol. 27; no. 12; pp. 1665 - 1676
• Main Authors: Kfoury, Y, Nasr, R, Favre-Bonvin, A, El-Sabban, M, Renault, N, Giron, M-L, Setterblad, N, Hajj, H El, Chiari, E, Mikati, A G, Hermine, O, Saib, A, de Thé, H, Pique, C, Bazarbachi, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.03.2008; Nature Publishing; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Apoptosis; Biological and medical sciences; Carrier Proteins - metabolism; Cell Biology; Cell cycle; Cell Line, Transformed; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Centrosome - metabolism; Centrosomes; DNA binding proteins; Enzyme Activation - physiology; Fundamental and applied biological sciences. Psychology; Gene Products, tax - metabolism; HeLa Cells; Human Genetics; Human T-lymphotropic virus 1; Human T-lymphotropic virus 1 - metabolism; Humans; I-kappa B Kinase - metabolism; IKK protein; Internal Medicine; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Molecular and cellular biology; NF-κB protein; Oncology; original-article; Physiological aspects; Proteasomes; Protein Binding; Protein kinases; Protein Subunits - metabolism; Proteins; Signal Transduction - physiology; Tax protein; Ubiquitin; Ubiquitin - metabolism; France; NF-κB; HTLV-I; Tax; centrosome; ubiquitin; IκB kinase; Ubiquitin; Deltaretrovirus; Enzyme; Transferases; Retroviridae; Carcinogenesis; Virus; Kinase; Transcription factor NFκB; HTLV-I virus; Centrosome
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210804

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.