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Survivin and Aurora B kinase, two targets in the search for anti - mitotic drugs; identification of a new class of Aurora kinase inhibitors.

Abstract : The chromosomal passenger complex (CPC) plays a key role in mitosis : controlling both chromosome segregation, spindle tension, anaphase onset and cytokinesis. The complex is composed of four proteins: INCENP, Aurora B kinase, Survivin and Borealin. Taking into account that Survivin is phosphorylated by Aurora B and has a pivotal role in the complex, we have studied the phosphomimetic mutant SurvivinT117E. Survivin phosphorylation is required for anaphase onset and the phospho-mutant is poorly linked to centromere. Moreover it exhibits a dominant negative function in cytokinesis, preventing abscission. In a search for Aurora kinase inhibitors we have identified a new class of Aurora B kinase inhibitors that prevents Histone H3 phosphorylation, impairs mitotic spindle checkpoint. Moreover these molecules prevent tumor cell proliferation. These inhibitors are interesting tools for understanding CPC function and represent a new lead for the development of anti-cancer drugs. Survivin and Aurora B kinase, which are expressed exclusively in mitosis, are thus two druggable targets for new anti-mitotic therapies.
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https://tel.archives-ouvertes.fr/tel-00398008
Contributor : Thi My Nhung Hoang <>
Submitted on : Monday, July 13, 2009 - 11:47:30 AM
Last modification on : Friday, November 6, 2020 - 4:12:32 AM
Long-term archiving on: : Wednesday, September 22, 2010 - 12:59:19 PM

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  • HAL Id : tel-00398008, version 2

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U823 | UGA

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Thi My-Nhung Hoang. Survivin and Aurora B kinase, two targets in the search for anti - mitotic drugs; identification of a new class of Aurora kinase inhibitors.. Life Sciences [q-bio]. Université Joseph-Fourier - Grenoble I, 2008. English. ⟨tel-00398008v2⟩

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