La mitose est précisément contrôlée par la signalisation via l'ubiquitine et est essentielle au maintien de l'intégrité du génome. Dans ce travail, j'ai étudié la fonction de l'enzyme de dé-ubiquitination, UCHL3 et de la ligase E3-ubiquitine, TRIM15. J'ai observé que TRIM15 régule l'adhésion et la mobilité des cellules. UCHL3 a été identifié par un criblage à haut contenu, en tant que facteur critique contrôlant l'alignement et la ségrégation des chromosomes. Fait intéressant, il a déjà été rapporté que les niveaux d’expression d’UCHL3 sont altérés dans divers types de cancer. En utilisant une approche protéomique, nous avons identifié la kinase Aurora B comme un médiateur potentiel de ces phénotypes. Comme l'aneuploïdie est la marque de nombreux cancers et que l'adhésion cellulaire joue un rôle important dans l'invasion des tumeurs et les métastases, mes résultats suggèrent que ces deux protéines pourraient jouer un rôle dans la carcinogenèse. / Mitosis is tightly controlled by ubiquitin signaling and is crucial to maintain genome integrity. In this work, I investigated the function of the deubiquitinating enzyme UCHL3 and the E3 ubiquitin ligase TRIM15. I observed that TRIM15 regulates cell adhesion and motility. UCHL3 was identified in a high-content screen, as a critical factor controlling the chromosome alignment and segregation. Interestingly, it has been previously reported that UCHL3 levels are altered in various cancer types. Using a proteomic approach, we identified Aurora B kinase as a potential mediator of these phenotypes. Since aneuploidy is a hallmark of many cancers, and cell adhesion plays an important role in tumor invasion and metastasis, my results suggest that both proteins could play a role in carcinogenesis.

(ENGLISH) Ubiquitin signaling is a key regulatory mechanism for many important cellular processes such as transcription, differentiation and cell division. Cell division requires duplication of all genetic material during S-phase followed by its precise partitioning between two daughter cells during mitosis. Misregulation of the complex mitotic machinery may lead to aneuploidy and genomic instability, known drivers of tumorigenesis. Indeed, systematic genetic analysis of many cancer tissues over the last decades, indicates the presence of severe chromosome abnormalities in thousands of cancer tissue samples. In this work, I investigated the function of two components of ubiquitin signaling, the deubiquitinating enzyme UCHL3 and the E3 ubiquitin ligase TRIM15. The hypothesized role of E3 ligase TRIM15 in the cell cycle regulation could not be confirmed by our experiments, but I observed an effect on cell adhesion and motility instead. UCHL3 was identified using high-content visual siRNA screen, as a critical factor controlling genome segregation and integrity. Interestingly, it has been previously reported that UCHL3 levels are altered in various cancer types, especially colon cancer. My data demonstrate that UCHL3 drives proper alignment of chromosomes at the metaphase plate by facilitating...