Reference : The HTLV-1 Tax protein inhibits formation of stress granules by interacting with histone...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/99149
The HTLV-1 Tax protein inhibits formation of stress granules by interacting with histone deacetylase 6.
English
Legros, S. [> > > >]
Boxus, Mathieu mailto [Université de Liège - ULg > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.]
Gatot, J. S. [> > > >]
Van Lint, C. [> > > >]
Kruys, V. [> > > >]
Kettmann, Richard mailto [Université de Liège - ULg > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.]
Twizere, Jean-Claude mailto [Université de Liège - ULg > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.]
Dequiedt, Franck mailto [Université de Liège - ULg > Giga-R > > >]
2011
Oncogene
Nature Publishing Group
Yes (verified by ORBi)
International
0950-9232
1476-5594
Basingstoke
United Kingdom
[en] virus ; mRNPs
[en] Human T cell leukemia virus type-1 (HTLV-1) is the causative agent of a fatal adult T-cell leukemia. Through deregulation of multiple cellular signaling pathways the viral Tax protein has a pivotal role in T-cell transformation. In response to stressful stimuli, cells mount a cellular stress response to limit the damage that environmental forces inflict on DNA or proteins. During stress response, cells postpone the translation of most cellular mRNAs, which are gathered into cytoplasmic mRNA-silencing foci called stress granules (SGs) and allocate their available resources towards the production of dedicated stress-management proteins. Here we demonstrate that Tax controls the formation of SGs and interferes with the cellular stress response pathway. In agreement with previous reports, we observed that Tax relocates from the nucleus to the cytoplasm in response to environmental stress. We found that the presence of Tax in the cytoplasm of stressed cells prevents the formation of SGs and counteracts the shutoff of specific host proteins. Unexpectedly, nuclear localization of Tax promotes spontaneous aggregation of SGs, even in the absence of stress. Mutant analysis revealed that the SG inhibitory capacity of Tax is independent of its transcriptional abilities but relies on its interaction with histone deacetylase 6, a critical component of SGs. Importantly, the stress-protective effect of Tax was also observed in the context of HTLV-1 infected cells, which were shown to be less prone to form SGs and undergo apoptosis under arsenite exposure. These observations identify Tax as the first virally encoded inhibitory component of SGs and unravel a new strategy developed by HTLV-1 to deregulate normal cell processes. We postulate that inhibition of the stress response pathway by Tax would favor cell survival under stressful conditions and may have an important role in HTLV-1-induced cellular transformation.Oncogene advance online publication, 2 May 2011; doi:10.1038/onc.2011.120.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/99149
10.1038/onc.2011.120

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