[en] HTLV-1 infects approximately 20 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 HTLV-1 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 ATM-Chk2-p53 axis 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 Chk2 and p53 checkpoints. This mechanism allows infected lymphocytes to proliferate despite the presence of genomic
lesions. Our data shows that HTLV-1 infected cells use an alternative DNA repair pathway controlled by ATM and Chk1. This particularity may be used as novel
therapeutic approach based on the principle of synthetic lethality.
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 :
Ckeckpoints modulation by Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax protein
Publication date :
05 December 2013
Event name :
Séminaire des Chercheurs Télévie 2014
Event organizer :
Université Catholique de Louvain (UCL) - Ecole Doctorale Thématique en Cancérologie Expérimentale