Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-kappa B pathway

作者：Lodewick Julie; Lamsoul Isabelle; Polania Angela; Lebrun Sylvie; Burny Arsene; Ratner Lee; Bex Francoise^*

来源：Virology, 2009, 386(1): 68-78.

DOI：10.1016/j.virol.2008.12.043

• HTLV-1
• Tax
• Acetylation
• CBP/p300
• NF-kappa B

The oncogenic potential of the HTLV-1 Tax protein involves activation of the NF-kappa B pathway, which depends on Tax phosphorylation, ubiquitination and sumoylation. We demonstrate that the nuclei of Tax-expressing cells, including HTLV-1 transformed T-lymphocytes, contain a pool of Tax molecules acetylated on lysine residue at amino acid position 346 by the transcriptional coactivator p300. Phosphorylation of Tax on serine residues 300/301 was a prerequisite for Tax localization in the nucleus and correlated with its subsequent acetylation by p300, whereas sumoylation, resulting in the formation of Tax nuclear bodies in which p300 was recruited, favored Tax acerylation. Overexpression of p300 markedly increased Tax acetylation and the ability of a wild type HTLV-1 provirus, -but not of a mutant provirus carrying an acetylation deficient Tax gene-, to activate gene expression from an integrated NF-kappa B-controlled promoter. Thus, Tax acetylation favors NF-kappa B activation and might play an important role in HTLV-1-induced cell transformation.

• 出版日期2009-3-30