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Etude des interactions entre la kinésine mitotique humaine Eg5 et ses inhibiteurs

Abstract : The human mitotic kinesin HsEg5 plays an essential role in cell division. This protein is required for the separation of the duplicated centrosomes and the formation of the mitotic spindle. Failure of HsEg5 function blocks centrosome migration and causes cells to arrest midway through mitosis with a characteristic monoastral spindle consisting of a radial array of microtubules surrounded by a ring of chromosomes. This particular phenotype can lead to cell death by the apoptotic pathway. HsEg5 is thus considered as a very promising target for cancer chemotherapy.
In this study, we investigate the binding regions of several inhibitors targeting the motor domain of HsEg5. These studies were carried out by using hydrogen/deuterium exchange – mass spectrometry and mutagenesis. Our experimental approach has been successfully applied to localize a “hot spot” binding region on the motor domain and to characterize the mechanism of HsEg5 inhibition by monastrol and S-trityl-l-cysteine.
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Contributor : Sebastien Brier <>
Submitted on : Tuesday, December 20, 2005 - 5:43:57 PM
Last modification on : Tuesday, October 6, 2020 - 4:12:03 PM
Long-term archiving on: : Saturday, April 3, 2010 - 7:43:31 PM


  • HAL Id : tel-00011246, version 1



Sebastien Brier. Etude des interactions entre la kinésine mitotique humaine Eg5 et ses inhibiteurs. Sciences du Vivant [q-bio]. Université Joseph-Fourier - Grenoble I, 2005. Français. ⟨tel-00011246⟩



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