Poster (Scientific congresses and symposiums)
Inhibition of Tax transformation activity using a small molecule targetting Tax/PDZ domain interactions.
Blibek, Karim; Fujii, Naoki; Legros, Sebastien et al.
201316th International Conference on Human Retrovirology : HTLV and Related Viruses.
 

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Keywords :
HTLV-1; Tax; PDZ; Transformation
Abstract :
[en] Primate T-lymphotropic virus species comprise four members (HTLV-1 to -4) that have been discovered in human. Only the HTLV-1 infection leads to adult T-cell leukemia/lymphoma (ATLL). All the four viruses share a similar genomic organization and encode transforming Tax oncoproteins. In contrast to HTLV-2 and 4, HTLV-1 and 3 Tax proteins contain a PSD-95/Drosophila Discs Large/Zona Occludens-I (PDZ) binding motif at their C-terminal that has been shown to play crucial roles in the distinct transforming properties of the Tax proteins. Here, we used a collection of human full-length protein-coding open reading frames (ORFeome v3.1) to identify novel PDZ domain containing proteins that specifically interact with HTLV-1 Tax. Novel Tax interactors include syntenin-1 and -2, LNX2, DVL3, GIPC2, INTU, PDLIM4 and -7, RADIL and RGS3. These proteins are involved in diverse biological processes including cell division, cell fate determination and cell suvival. We further characterized interaction between Tax and syntenins and showed that, FJ9 a small molecule able to disrupt Tax/PDZ interactions, could antagonize Tax-transformation activity in rat-1 model. Our study identify novel PDZ-containg proteins interacting with HTLV-1 Tax and provides the first example where Tax protein-protein interactions whith PDZ-containing proteins and Tax-transformation capacity could be inhibited by a small molecule.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Blibek, Karim ;  Université de Liège - ULiège > GIGA - Membres
Fujii, Naoki
Legros, Sebastien
Boxus, Mathieu
Dewulf, Jean-François
Zimmermann, Pascale
Kettmann, Richard
Borg, Jean-Paul
Dequiedt, Franck  ;  Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Twizere, Jean-Claude  ;  Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Language :
English
Title :
Inhibition of Tax transformation activity using a small molecule targetting Tax/PDZ domain interactions.
Alternative titles :
[en] Inhibition de l'activité transformante de Tax avec une petite molecule ciblant les interactions Tax/PDZ.
Publication date :
29 June 2013
Number of pages :
A1
Event name :
16th International Conference on Human Retrovirology : HTLV and Related Viruses.
Event organizer :
Université de Montréal
Université du Québec à Montréal-UQAM
Event place :
Montréal, Québec., Canada
Event date :
du 26 Juin au 30 Juin 2013.
By request :
Yes
Audience :
International
Name of the research project :
Etude du rôle des protéines à domaines PDZ dans l'infection et la transformation des lymphocytes T par le virus de la leucémie humaine HTLV-1.
Funders :
ULiège - Université de Liège [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
Available on ORBi :
since 06 August 2013

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