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Étude structurale et fonctionnelle des propriétés d'interaction à l'ubiquitine de la protéine CEP55, un régulateur essentiel de la cytocinèse

Abstract : CEP55 (Centrosomal protein 55 KDa) critically regulates the final step of cell division termed cytokinesis. In the first part, using bioinformatical, structure-function and cell biology approaches, we showed that CEP55 contains two new NEMO-like ubiquitin binding domains, NOACEP55 and ZFCEP55, which differentially regulate CEP55 function during cytokinesis. Structural modeling, mutagenesis and biophysical studies of both domains pointed out that NOACEP55 adopts a dimeric coiled-coil structure and selectively interacts with linear ubiquitin chains (M1). However, ZFCEP55 presents a zinc-finger scaffold – or UBZ – and preferentially binds to K63 and M1 ubiquitin chains. Moreover, our results highlight that ZFCEP55 functions as a cargo receptor to the midbody in an ubiquitin dependent manner whilst NOACEP55 plays a crucial role in cytokinesis but acts downstream of CEP55 recruitment to the midbody. In the second part, we showed that NOACEP55 and ZFCEP55 separated by a proline rich linker cooperatively interact with long K63 poly-ubiquitin chains and this interaction can be modulated by phosphorylation and isomerization via CEP55 physiological partners. Finally, these results allowed us to identify E3-ligases and deubiquitinases involved in cytokinesis, which permit to discuss the role of ubiquitin signaling in this cellular process.
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  • HAL Id : tel-01954487, version 1

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Keis Nabhane Said Halidi. Étude structurale et fonctionnelle des propriétés d'interaction à l'ubiquitine de la protéine CEP55, un régulateur essentiel de la cytocinèse. Biochimie [q-bio.BM]. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066609⟩. ⟨tel-01954487⟩

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