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

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 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-{kappa}B-controlled promoter. Thus, Tax acetylation favors NF-{kappa}B activation and might play an important role in HTLV-1-induced cell transformation.
Authors:
; ; ;  [1] ;  [2] ;  [3] ;  [4]
  1. Institute for Microbiological Research J-M Wiame and Laboratory of Microbiology, Universite Libre de Bruxelles, 1, Avenue Emile Gryson, B-1070 Brussels (Belgium)
  2. Faculte des Sciences Agronomiques de Gembloux, Gembloux (Belgium)
  3. Division of Molecular Oncology, Washington University School of Medicine, St Louis (United States)
  4. Institute for Microbiological Research J-M Wiame and Laboratory of Microbiology, Universite Libre de Bruxelles, 1, Avenue Emile Gryson, B-1070 Brussels (Belgium), E-mail: fbex@ulb.ac.be
Publication Date:
OSTI Identifier:
21182815
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 386; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2008.12.043; PII: S0042-6822(09)00009-9; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLATION; CELL TRANSFORMATIONS; GENES; LEUKEMIA VIRUSES; LYMPHOCYTES; LYSINE; MOLECULES; MUTANTS; PHOSPHORYLATION; PROTEINS; SERINE