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Étude fonctionnelle de la sous-unité régulatrice de la protéine kinase CK2 dans les cellules souches embryonnaires murines : survie cellulaire, oligodendrogenèse et cancérogenèse.

Abstract : The protein kinase CK2 is a dynamic molecular complex of 2 catalytic subunits α and of a dimer of regulatory subunit β. Cristallographic structure of the CK2β dimer suggests the existence of functional domains involved in the regulating function of the dimer towards the catalytic subunits, as well as in interactions with various protein partners. The CK2β dimer would represent a molecular platform, linking the protein to the center of signalling pathway networks.
The knockout of the murin CK2β gene results in a defect of embryonic stem cell viability. We studied the in vitro function of different functional domains with the use of a “death-rescue” cellular model of by additional transgenesis of mutants CK2β. This cellular system is based on a conditional CK2β gene knockout strategy using murin embryonic stem cells (ES cells). The abolition of the endogenous gene expression is lethal for ES cells and the exogenous expression of the wild-type protein CK2β rescues their viability. This “death-rescue” model allows us to study the involvement of various domains of CK2β in the survival, the proliferation and the differentiation of embryonic stem cells.
In parallel, the conditional targeted knockout in murin neural precursors demonstrated that CK2β is a key element in signalling pathways that control oligodendrogenesis. The differentiation of nullizygotes ES cells expressing the wild-type exogenous protein reveals that wild-type CK2β rescues the oligodendrocyte lineage. We also showed that some CK2β domains, linked to dimer regulatory functions, are crucial structural determinants for the proliferation of neural stem cells and their progression into the oligodendrocyte lineage.
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https://tel.archives-ouvertes.fr/tel-00188215
Contributor : Léa Ziercher <>
Submitted on : Friday, November 16, 2007 - 9:13:26 AM
Last modification on : Friday, November 6, 2020 - 4:07:49 AM
Long-term archiving on: : Friday, November 25, 2016 - 7:13:16 PM

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  • HAL Id : tel-00188215, version 1

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Léa Ziercher. Étude fonctionnelle de la sous-unité régulatrice de la protéine kinase CK2 dans les cellules souches embryonnaires murines : survie cellulaire, oligodendrogenèse et cancérogenèse.. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00188215⟩

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