Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome.
Constitutive activation of the NF-kappaB 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 IkappaB 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.
Kfoury
Y
Y
Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
Nasr
R
R
Favre-Bonvin
A
A
El-Sabban
M
M
Renault
N
N
Giron
M-L
ML
Setterblad
N
N
Hajj
H El
HE
Chiari
E
E
Mikati
A G
AG
Hermine
O
O
Saib
A
A
de Thé
H
H
Pique
C
C
Bazarbachi
A
A
D002352:Carrier Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D018385:Centrosome / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D016356:Gene Products, tax / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D035602:Transcriptional Elongation Factors; D025801:Ubiquitin / Q000378:metabolism*
D002352:Carrier Proteins; C114720:Elp1 protein, human; D016356:Gene Products, tax; C491731:IKBKG protein, human; D021122:Protein Subunits; D035602:Transcriptional Elongation Factors; D025801:Ubiquitin; D051550:I-kappa B Kinase; C496560:IKBKB protein, human