Skip to Main content Skip to Navigation
Master Thesis

Identification et caractérisation des partenaires cellulaires de zebra, facteur de transcription du virus Epstein-Barr : mise en évidence d'un complexe tripartite entre la protéine virale zebra et les protéines cellulaires ubinucléine et 14-3-3epsilon

Abstract : Epstein-Barr Virus (EBV) has a prevalence of 95% in the worldwide population. It is known for its oncogenicity and its association with lymphoma and epithelial cancer. ZEBRA is a viral transcription factor playing a key role in viral reactivation and EBV-associated oncogenicity. Previous studies described a cellular protein named Ubinuclein (Ubn), capable of preventing ZEBRA's binding on its DNA target sequences. Our laboratory has shown that Ubn can be localized either in the nucleus or in the tight junctions of the cells. It is very likely that the Ubn's travelling involves other cellular proteins and we focused on the 14-3-3 protein family, which is well known to regulate the nucleus import/export of numerous proteins. The purpose of this work is to better understand the conditions in which Ubn inhibits ZEBRA's functions and the viral lytic cycle. We hypothesized that, by controlling Ubn's cellular localization, 14-3-3epsilon could regulate the Ubn-ZEBRA interaction. In vivo and in vitro technics (immunoprecipitation, pull-down, immunofluorescence) allowed us to demonstrate the existence of a ternary complex between ZEBRA, Ubn and 14-3-3epsilon and to show that Ubn plays the role of an intermediate between its two partners. More precisely, 14-3-3epsilon binds to Ubn on a consensus motif containing a phosphorylated serine. The study of Ubn's phosphorylation revealed that non-phosphorylated Ubn is localized preferentially at the tight junctions. Taken together, all these experiments suggest that 14-3-3epsilon could promote the nuclear localization of Ubn, allowing it to interact with ZEBRA and preventing EBV's lytic cycle initiation.
Document type :
Master Thesis
Complete list of metadata

Cited literature [103 references]  Display  Hide  Download

https://dumas.ccsd.cnrs.fr/dumas-00653237
Contributor : Jean-Hugues Morneau <>
Submitted on : Monday, December 19, 2011 - 10:22:46 AM
Last modification on : Tuesday, May 11, 2021 - 11:36:17 AM
Long-term archiving on: : Monday, December 5, 2016 - 2:52:28 AM

Identifiers

  • HAL Id : dumas-00653237, version 1

Citation

Charlotte Sueur. Identification et caractérisation des partenaires cellulaires de zebra, facteur de transcription du virus Epstein-Barr : mise en évidence d'un complexe tripartite entre la protéine virale zebra et les protéines cellulaires ubinucléine et 14-3-3epsilon. Sciences pharmaceutiques. 2011. ⟨dumas-00653237⟩

Share

Metrics

Record views

197

Files downloads

832