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Theses

Mécanisme de contrôle de l'entrée en mitose par Polo-like kinase 1 (PlK1)

Abstract : A main requirement of the cell cycle is a tight coordination between the completion of the replication process and entry into mitosis in order to maintain genetic integrity and the identity and survival of cell progeny. All somatic cells reproducibly execute an intermediate G2 phase of constant duration during successive cell divisions in a given cell type. However the molecular mechanisms controlling precisely its duration during unperturbed cell cycle remains poorly characterized. In this context, the main objective of my PhD project was to decipher signaling pathways controlling entry into mitosis during normal cell cycles as well as their spatiotemporal regulation. CyclinB1-Cdk1, the universal master mitotic driver, is under the control of direct inhibitors (Wee1 and Myt1) and activators (Cdc25A, B and C). Previously, it was determined that CyclinB1-Cdk1 is suddenly activated in very late G2 phase, suggesting that a rapid modification in the equilibrium between its opposite regulators is reproducibly taking place in late G2 by poorly elucidated mechanisms. During my PhD, I investigated the potential role of Polo-like kinase 1 (Plk1) in the initial activation of CyclinB1-Cdk1. Even though its roles during mitosis are well characterized, its contribution for the regulation of entry into mitosis remains controversial. At the molecular level, Plk1 was shown to phosphorylate at least in vitro, several regulators of CyclinB1-Cdk1 including Cdc25B&C, and Wee1 and Myt1. However, it remains largely unknown if these phosphorylation events are taking place in vivo and whether they significantly contribute to the activation process of CyclinB1-Cdk1 leading to mitotic entry.
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Submitted on : Tuesday, March 27, 2018 - 12:18:42 PM
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  • HAL Id : tel-01744330, version 1

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Lilia Gheghiani. Mécanisme de contrôle de l'entrée en mitose par Polo-like kinase 1 (PlK1). Biologie cellulaire. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066385⟩. ⟨tel-01744330⟩

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