Monnerat, S., Almeida Costa, C.I., Forkert, A.C., Benz, C., Hamilton, A., Tetley, L., Burchmore, R. , Novo, C., Mottram, J.C. and Hammarton, T.C. (2013) Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei. PLoS ONE, 8(6), e67327. (doi: 10.1371/journal.pone.0067327) (PMID:23805309) (PMCID:PMC3689728)
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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0067327
Abstract
The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Tetley, Dr Laurence and Burchmore, Dr Richard and Benz, Dr Corinna and Hammarton, Dr Tansy and Hamilton, Mrs Alana and Mottram, Professor Jeremy |
| Authors: | Monnerat, S., Almeida Costa, C.I., Forkert, A.C., Benz, C., Hamilton, A., Tetley, L., Burchmore, R., Novo, C., Mottram, J.C., and Hammarton, T.C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | PLoS ONE |
| Publisher: | Public Library of Science |
| ISSN: | 1932-6203 |
| ISSN (Online): | 1932-6203 |
| Copyright Holders: | Copyright © 2013 The Authors |
| First Published: | First published in PLoS ONE 8(6):e67327 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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