Article (Scientific journals)
The HTLV-1 Tax protein inhibits formation of stress granules by interacting with histone deacetylase 6.
Legros, S.; Boxus, Mathieu; GATOT, Jean-Stéphane et al.
2011In Oncogene
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Keywords :
virus; mRNPs
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Legros, S.
Boxus, Mathieu ;  Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.
GATOT, Jean-Stéphane 
Van Lint, C.
Kruys, V.
Kettmann, Richard ;  Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.
Twizere, Jean-Claude  ;  Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.
Dequiedt, Franck  ;  Université de Liège - ULiège > Giga-R
Language :
English
Title :
The HTLV-1 Tax protein inhibits formation of stress granules by interacting with histone deacetylase 6.
Publication date :
2011
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, Basingstoke, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 September 2011

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