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Analyse de la régulation du facteur de transcription E2F1 par cIAP1

Abstract : The cellular inhibitor of Apoptosis 1 (cIAP1) behaves as an E3 ubiquitin ligase and has oncogenic properties. Previously, our team has shown that cIAP1 can regulate the E2F1 transcription factor activity. My research project has been focused on deepening our current knowledge on this interaction. Firstly, we characterized the E2F1-cIAP1 interaction, then we analyzed the regulation of E2F1 by cIAP1 and finally assessed the importance of the cIAP1-E2F1 interaction for the oncogenic properties of cIAP1. I have demonstrated a interaction of E2F1 with the hydrophobic pocket of the BIR3 domain of cIAP1. Moreover, I highlighted that the alpha 1 helix of the BIR3 domain is mandatory for the stability of this pocket. Moreover, we discovered an ubiquitination on lysine 161 and 164 of E2F1 by cIAP1. This ubiquitination is essential for the stability and transcriptional activity of E2F1. Finally, it appears that the cIAP1 BIR1 domain that is required for the interaction with TRAF2 is involved in its oncogenic properties.
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Submitted on : Tuesday, April 16, 2019 - 4:44:08 PM
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  • HAL Id : tel-02101414, version 1

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Jennifer Allègre-Cultot. Analyse de la régulation du facteur de transcription E2F1 par cIAP1. Sciences agricoles. Université Bourgogne Franche-Comté, 2017. Français. ⟨NNT : 2017UBFCI013⟩. ⟨tel-02101414⟩

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