DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2010-09-04 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Bazot Quentin, Tafforeau Lionel , Rabourdin-Combe Chantal, Lotteau Vincent, Gruffat Henri, Manet Evelyne, "EBNA3A represses CDKN2A and CDKN2B expression through interaction with MIZ-1" in 14th Biennal Conference of the International Association for Research on Epstein-Barr Virus & Associated Diseases, Birmingham, UK, 2010

  • Codes CREF : Biologie (DI3100)
  • Unités de recherche UMONS : Biologie cellulaire (S815)
  • Instituts UMONS : Institut des Biosciences (Biosciences)

Abstract(s) :

(Anglais) The Epstein-Barr virus (EBV) nuclear antigen 3A (EBNA-3A) is one of the essential latent proteins necessary for primary B-cell transformation. The exact role of EBNA-3A is not yet completely understood. To better understand the function of the protein, we searched for EBNA3A interacting partners using a yeast two-hybrid screen. One of the proteins identified in this screen is the Myc-interacting zinc finger protein-1 (Miz-1), a transcription factor initialy characterized as a binding partner of c-Myc. Miz-1 has a cell growth arrest activity via inhibition of cell-cycle progression and has been shown to activate transcription of target genes including CDKN1A and CDKN2B. We first confirmed the interaction between EBNA- 3A and Miz-1 by co-immunoprecipitation assays in HeLa cells transiently transfected with EBNA-3A and Miz-1 expression vectors. Then we established the physiological relevance of the interaction by showing that EBNA-3A and Miz-1 could be co-immunoprecipitated from a lymphoblastoid cell line (LCL) expressing endogenous EBNA-3A and Miz-1. We next investigated the effect of EBNA-3A on Miz-1-mediated activation of CDKN2A and CDKN2B. HeLa cells were transfected with luciferase reporter constructs containing the human CDKN2A or CDKN2B promoters, in the presence of Miz-1 alone or Miz-1 plus EBNA-3A. Interestingly, we found that expression of EBNA-3A inhibits Miz-1 dependant activation of both CDKN2A and CDKN2B promoters in a dose-dependant manner. The interaction between EBNA-3A and Miz-1 is thus likely to play an essential role in EBV dependant transformation of primary B cells. The mechanisms of inhibition of Miz-1 dependant activation by EBNA-3A will be discussed.