Modulation de la machinerie de O-GlcNACylation par l’oncoprotéineTax du virus HTLV-1 et implication dans la transactivation du promoteur viral

Abstract : HTLV-1 virus is the only oncogenic human retrovirus discovered to date. It is responsible for a T cell malignant lymphoproliferation named Adult T cell Leukemia. HTLV-1 Tax oncoprotein plays a major role in the development of the leukemia and also in the viral replication. Tax regulates the transcription from the viral promoter located in the virus 5’LTR, favoring its own transcription. In order to do this, Tax recrutes dimers of the phosphorylated cellular transcription factor CREB to viral cyclic AMP response elements (vCRE) situated in the U3 part of the LTR. CREB phosphorylation is a crucial process to allow the transactivation of the viral promoter. CREB is also targeted and regulated by OGlcNAcylation which is a post-translational modification implicated in many pathologies such as cancer. Its regulation depends on two enzymes, OGA and OGT forming the OGlcNAzyme complex. As Tax deregulates many post-translational modification machineries and as OGlcNAcylation regulates the stability and activity of transcriptional factors together with phosphorylation, we have evaluated for the first time the OGlcNAcylation status of CREB in the context of HTLV-1 infection and its implication in the regulation of the viral promoter. We have shown that in the context of HTLV-1 infection, Tax protein was deregulating the OGlcNAcylation machinery leading to an increase in CREB OGlcNAcylation which favors the transcription from the 5’LTR. Thus we have established for the first time a relationship between Tax and OGlcNAcylation allowing us to propose a new model of regulation of the viral LTR.
Keywords : Virology
Document type :
Theses
Complete list of metadatas

Cited literature [460 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-02141273
Contributor : Abes Star <>
Submitted on : Monday, May 27, 2019 - 5:40:07 PM
Last modification on : Saturday, June 15, 2019 - 4:29:15 AM

File

va_Groussaud_Damien.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-02141273, version 1

Collections

Citation

Damien Groussaud. Modulation de la machinerie de O-GlcNACylation par l’oncoprotéineTax du virus HTLV-1 et implication dans la transactivation du promoteur viral. Virologie. Université Sorbonne Paris Cité, 2016. Français. ⟨NNT : 2016USPCB252⟩. ⟨tel-02141273⟩

Share

Metrics

Record views

200

Files downloads

96