Skip to Main content Skip to Navigation
New interface
Theses

Etude des fonctions des protéines virales de la famille EBNA3 dans l'immortalisation des lymphocytes B par le virus d'Epstein-Barr : rôle fonctionnel de l'interaction entre EBNA-3A et la protéine cellulaire Miz-1

Abstract : Epstein-Barr Virus (EBV) is a human Herpesvirus that infects over 90% of the world population and is associated with several malignancies. EBV has the unique capacity to activate and to induce growth transformation of resting primary human B-lymphocytes, upon their in vitro infection, leading to the establishment of lymphoblastoid cell lines (LCLs). In these cells (called Lymphoblatoid cell lines (LCLs)), nine latent proteins are expressed driving the activation and proliferation of the infected B cells. In order to understand the molecular mechanism by which the EBNA3s latent proteins play a role in growth transformation, we used a large scale two-hybrid yeast screen. Thanks to that screen we identified several cellular partners very interesting in relation to what we know about the EBNA3s functions. One of the proteins identified in this screen is the transcription factor Miz-1, which has a cell growth arrest activity via inhibition of cell-cycle progression and has been shown to activate transcription of target genes including CDKN1A, CDKN1C and CDKN2B. We confirmed the interaction between EBNA-3A and Miz-1 by GST-pull down assay as well as by co-immunoprecipitation in HeLa cells We next investigated the effect of EBNA-3A on Miz-1-dependent regulation by comparing the transcript levels of selected Miz-1 target genes between EBNA-3A positive and negative LCLs by RT-qPCR. Interestingly, several Miz-1 target genes, among which CDKN2B, were found to be differentialy regulated in the presence of EBNA-3A. We found that EBNA-3A inhibits Miz-1 dependant activation by inhibiting the recrutement of the co-activator NPM. Those results bring new insights to the mechanisms by which the EBNA3s, and more largely EBV, regulate the cell cycle.
Complete list of metadata

https://tel.archives-ouvertes.fr/tel-00923179
Contributor : ABES STAR :  Contact
Submitted on : Thursday, January 2, 2014 - 2:10:34 AM
Last modification on : Thursday, April 9, 2020 - 3:36:18 AM
Long-term archiving on: : Saturday, April 8, 2017 - 9:15:15 AM

File

BAZOT_Quentin_2012_These_-_.pd...
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00923179, version 1

Collections

Citation

Quentin Bazot. Etude des fonctions des protéines virales de la famille EBNA3 dans l'immortalisation des lymphocytes B par le virus d'Epstein-Barr : rôle fonctionnel de l'interaction entre EBNA-3A et la protéine cellulaire Miz-1. Biologie moléculaire. Ecole normale supérieure de lyon - ENS LYON, 2012. Français. ⟨NNT : 2012ENSL0770⟩. ⟨tel-00923179⟩

Share

Metrics

Record views

568

Files downloads

129