Poster (Scientific congresses and symposiums)
Checkpoints modulation by the human T-lymphotropic virus type 1 (HTLV-1) Tax protein : towards new therapeutic approaches
Carpentier, Alexandre; Barez, Pierre-Yves; Boxus, Mathieu et al.
2015GIGA Cancer Day 2015
 

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Keywords :
HTLV-1; Tax; DNA Damage
Abstract :
[en] HTLV-1 infects approximately 15 million people worldwide and causes several diseases. This virus is responsible for the adult T-cell leukemia (ATL) and for a chronic neuropathology (TSP/HAM). There is currently no satisfactory treatment for these diseases. 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 the Tax viral oncoprotein. In particular, we aim at understanding the interplay between Tax and the DNA damage response (DDR). We show 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. In contrast, HTLV-1 infected lymphocytes proliferate continuously and appear to be adapted to the checkpoints. This mechanism of checkpoint adaptation thus allows ongoing proliferation despite the presence of genomic lesions. Quantification of the rates of NHEJ and homologous recombination indicates that HTLV-1 infected cells require very efficient DNA repair for survival. Therefore, we propose a novel therapeutic approach based on the principle of synthetic lethality using inhibitors of DNA repair.
Disciplines :
Oncology
Author, co-author :
Carpentier, Alexandre ;  Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Barez, Pierre-Yves ;  Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Boxus, Mathieu
Willems, Luc  ;  Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Language :
English
Title :
Checkpoints modulation by the human T-lymphotropic virus type 1 (HTLV-1) Tax protein : towards new therapeutic approaches
Publication date :
13 May 2015
Number of pages :
A0
Event name :
GIGA Cancer Day 2015
Event organizer :
Ecole Doctorale en Cancérologie Exprériementale & GIGA Cancer
Event place :
Liège, Belgium
Event date :
13 mai 2015
Available on ORBi :
since 22 May 2015

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