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Comparative analysis of HTLV-1 and HTLV-2 post-translational modifications of Tax proteins in relation to their intracellular localization and activation of gene expression
Retrovirologyvolume 6, Article number: P87 (2009)
The functional analysis of regulatory proteins Tax-1 and Tax-2 can provide useful information to further understand the difference in pathogenicity between HTLV-1 and HTLV-2.
Tax-1 molecules phosphorylated at serine residues 300 and 301, ubiquitinated or sumoylated at lysine residues 280 and 284 and acetylated at lysine 346 have been identified. These modifications control Tax-1 intracellular localization, the formation of Tax-1 nuclear bodies and sequential steps in Tax-1-mediated activation of the NF-κB pathway, a critical event thought to be involved in HTLV-1 transforming capacity .
By comparing internally tagged Tax-1 and Tax-2B, we demonstrated that Tax-2B activates gene expression via the NF-κB pathway, is present in nuclear bodies and in the cytoplasm and is modified by ubiquitination and sumoylation similarly to its homologue Tax-1 .
In the present study, we constructed a series of Tax-2B mutants with substitutions of specific lysine residues by arginines. The post-translational modifications, subcellular localization and capacity to activate gene expression of these Tax-2B mutants will be compared to those obtained for the corresponding mutants of Tax-1.
Lamsoul I, Lodewick J, Lebrun S, Brasseur R, Burny A, Gaynor RB, Bex F: Exclusive ubiquitination and sumoylation on overlapping lysine residues mediate NF-kappaB activation by the human T-cell leukemia virus tax oncoprotein. Mol Cell Biol. 2005, 25: 10391-10406. 10.1128/MCB.25.23.10391-10406.2005.
Turci M, Lodewick J, Righi P, Polania A, Romanelli MG, Bex F, Bertazzoni U: HTLV-2B Tax oncoprotein is modified by ubiquitination and sumoylation and displays intracellular localization similar to its homologue HTLV-1 Tax. Virology. 2009