Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-kappaB pathway.
The oncogenic potential of the HTLV-1 Tax protein involves activation of the NF-kappaB 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 acetylation. 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-kappaB-controlled promoter. Thus, Tax acetylation favors NF-kappaB activation and might play an important role in HTLV-1-induced cell transformation.
Lodewick
Julie
J
Institute for Microbiological Research J-M Wiame and Laboratory of Microbiology, Université Libre de Bruxelles, 1, Avenue Emile Gryson, B-1070 Brussels, Belgium.
Lamsoul
Isabelle
I
Polania
Angela
A
Lebrun
Sylvie
S
Burny
Arsène
A
Ratner
Lee
L
Bex
Françoise
F
D000107:Acetylation; D002467:Cell Nucleus / Q000737:chemistry; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D016356:Gene Products, tax / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation
D016356:Gene Products, tax; D016328:NF-kappa B; C514970:tax protein, Human T-lymphotrophic virus 1; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human