Article (Scientific journals)
Checkpoints modulation by the Human T-lymphotropic virus type 1 Tax protein
Carpentier, Alexandre; Barez, Pierre-Yves; Boxus, Mathieu et al.
2014In Retrovirology, 11 (S1), p. 90
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Keywords :
HTLV-1; Tax; DNA Damage Response (DDR); Genomic stress; Synthetic lethality
Abstract :
[en] HTLV-1 is responsible for two main diseases, Adult T-cell Leukemia/Lymphoma and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis, for which there is currently no satisfactory treatment. Among the proteins encoded by HTLV-1, Tax appears to play an important role in the mechanisms leading to pathogenicity. We are interested in the mechanisms of cell transformation by Tax and more particularly in the interplay between the viral Tax oncoprotein and the DNA damage response (DDR). We demonstrated that transient expression of Tax results in DNA damage, cell cycle arrest and activation of the DDR. In fibroblasts, cell cycle arrest occurs at the G1 and G2 phases depending on the p53 background. Although Tax induces apoptosis and senescence in fibroblasts, HTLV-1 infected lymphocytes proliferate continuously and appear to be adapted to the checkpoint control. This mechanism allows infected lymphocytes to proliferate despite the presence of genomic lesions. With these observations, we propose a novel therapeutic approach based on the principle of synthetic lethality.
Disciplines :
Oncology
Author, co-author :
Carpentier, Alexandre ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Barez, Pierre-Yves ;  Université de Liège - ULiège > Doct. sc. agro. & ingé. biol.
Boxus, Mathieu
Willems, Luc  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Language :
English
Title :
Checkpoints modulation by the Human T-lymphotropic virus type 1 Tax protein
Publication date :
2014
Journal title :
Retrovirology
eISSN :
1742-4690
Publisher :
BioMed Central, London, United Kingdom
Volume :
11
Issue :
S1
Pages :
90
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 January 2014

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