Please be advised that the site will be down for maintenance on Sunday, September 1, 2024, from 08:00 to 18:00, and again on Monday, September 2, 2024, from 08:00 to 09:00. We apologize for any inconvenience this may cause.
dc.contributor.author | Morahan, Belinda J.![]() |
|
dc.contributor.author | Abrie, Clarissa![]() |
|
dc.contributor.author | Al-Hasani, Keith![]() |
|
dc.contributor.author | Batty, Mitchell B.![]() |
|
dc.contributor.author | Corey, Victoria![]() |
|
dc.contributor.author | Cowell, Anne N.![]() |
|
dc.contributor.author | Niemand, Jandeli![]() |
|
dc.contributor.author | Winzeler, Elizabeth A.![]() |
|
dc.contributor.author | Birkholtz, Lyn-Marie![]() |
|
dc.contributor.author | Doerig, Christian![]() |
|
dc.contributor.author | Garcia-Bustos, Jose F.![]() |
|
dc.date.accessioned | 2021-02-26T14:57:26Z | |
dc.date.available | 2021-02-26T14:57:26Z | |
dc.date.issued | 2020-11 | |
dc.description.abstract | Mitosis has been validated by numerous anti-cancer drugs as being a druggable process, and selective inhibition of parasite proliferation provides an obvious opportunity for therapeutic intervention against malaria. Mitosis is controlled through the interplay between several protein kinases and phosphatases. We show here that inhibitors of human mitotic kinases belonging to the Aurora family inhibit P. falciparum proliferation in vitro with various potencies, and that a genetic selection for mutant parasites resistant to one of the drugs, Hesperadin, identifies a resistance mechanism mediated by a member of a different kinase family, PfNek1 (PF3D7_1228300). Intriguingly, loss of PfNek1 catalytic activity provides protection against drug action. This points to an undescribed functional interaction between Ark and Nek kinases and shows that existing inhibitors can be used to validate additional essential and druggable kinase functions in the parasite. | en_ZA |
dc.description.department | Biochemistry | en_ZA |
dc.description.department | Genetics | en_ZA |
dc.description.department | Microbiology and Plant Pathology | en_ZA |
dc.description.librarian | pm2021 | en_ZA |
dc.description.sponsorship | Larkins Fellowship, NIH, MMV, Bill and Melinda Gates Foundation, Medical Research Council and South African Research Chairs Initiative of the Department of Science and Technology. | en_ZA |
dc.description.uri | https://www.nature.com/commsbio | en_ZA |
dc.identifier.citation | Morahan, B.J., Abrie, C., Al-Hasani, K. et al. Human Aurora kinase inhibitor Hesperadin reveals epistatic interaction between Plasmodium falciparum PfArk1 and PfNek1 kinases. Communications Biology 3, 701 (2020). https://doi.org/10.1038/s42003-020-01424-z. | en_ZA |
dc.identifier.issn | 2399-3642 (online) | |
dc.identifier.other | 10.1038/s42003-020-01424-z | |
dc.identifier.uri | http://hdl.handle.net/2263/78874 | |
dc.language.iso | en | en_ZA |
dc.publisher | Nature Research | en_ZA |
dc.rights | © The Author(s) 2020. Open Access, this article is licensed under a Creative Commons Attribution 4.0 International License. | en_ZA |
dc.subject | Chemical genetics | en_ZA |
dc.subject | Target identification | en_ZA |
dc.subject | Human mitotic kinases | en_ZA |
dc.subject | Aurora kinase inhibitor | en_ZA |
dc.subject | Hesperadin | en_ZA |
dc.subject | Plasmodium falciparum | en_ZA |
dc.title | Human Aurora kinase inhibitor Hesperadin reveals epistatic interaction between Plasmodium falciparum PfArk1 and PfNek1 kinases | en_ZA |
dc.type | Article | en_ZA |