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Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome.

Publication ,  Journal Article
Kfoury, Y; Nasr, R; Favre-Bonvin, A; El-Sabban, M; Renault, N; Giron, M-L; Setterblad, N; Hajj, HE; Chiari, E; Mikati, AG; Hermine, O; Saib, A ...
Published in: Oncogene
March 13, 2008

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.

Duke Scholars

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

March 13, 2008

Volume

27

Issue

12

Start / End Page

1665 / 1676

Location

England

Related Subject Headings

  • Ubiquitin
  • Transcriptional Elongation Factors
  • Signal Transduction
  • Protein Subunits
  • Protein Binding
  • Oncology & Carcinogenesis
  • I-kappa B Kinase
  • Humans
  • Human T-lymphotropic virus 1
  • Hela Cells
 

Citation

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Kfoury, Y., Nasr, R., Favre-Bonvin, A., El-Sabban, M., Renault, N., Giron, M.-L., … Bazarbachi, A. (2008). Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome. Oncogene, 27(12), 1665–1676. https://doi.org/10.1038/sj.onc.1210804
Kfoury, Y., R. Nasr, A. Favre-Bonvin, M. El-Sabban, N. Renault, M. -. L. Giron, N. Setterblad, et al. “Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome.Oncogene 27, no. 12 (March 13, 2008): 1665–76. https://doi.org/10.1038/sj.onc.1210804.
Kfoury Y, Nasr R, Favre-Bonvin A, El-Sabban M, Renault N, Giron M-L, et al. Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome. Oncogene. 2008 Mar 13;27(12):1665–76.
Kfoury, Y., et al. “Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome.Oncogene, vol. 27, no. 12, Mar. 2008, pp. 1665–76. Pubmed, doi:10.1038/sj.onc.1210804.
Kfoury Y, Nasr R, Favre-Bonvin A, El-Sabban M, Renault N, Giron M-L, Setterblad N, Hajj HE, Chiari E, Mikati AG, Hermine O, Saib A, de Thé H, Pique C, Bazarbachi A. Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome. Oncogene. 2008 Mar 13;27(12):1665–1676.

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

March 13, 2008

Volume

27

Issue

12

Start / End Page

1665 / 1676

Location

England

Related Subject Headings

  • Ubiquitin
  • Transcriptional Elongation Factors
  • Signal Transduction
  • Protein Subunits
  • Protein Binding
  • Oncology & Carcinogenesis
  • I-kappa B Kinase
  • Humans
  • Human T-lymphotropic virus 1
  • Hela Cells