Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei.
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 celle...
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2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0067327&type=printable |
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| author | Séverine Monnerat Cristina I Almeida Costa Andrea C Forkert Corinna Benz Alana Hamilton Laurence Tetley Richard Burchmore Carlos Novo Jeremy C Mottram Tansy C Hammarton |
| author_facet | Séverine Monnerat Cristina I Almeida Costa Andrea C Forkert Corinna Benz Alana Hamilton Laurence Tetley Richard Burchmore Carlos Novo Jeremy C Mottram Tansy C Hammarton |
| author_sort | Séverine Monnerat |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6ca3f43ad432479ba236337bddf3ee1c |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-6ca3f43ad432479ba236337bddf3ee1c2025-08-20T03:26:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6732710.1371/journal.pone.0067327Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei.Séverine MonneratCristina I Almeida CostaAndrea C ForkertCorinna BenzAlana HamiltonLaurence TetleyRichard BurchmoreCarlos NovoJeremy C MottramTansy C HammartonThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0067327&type=printable |
| spellingShingle | Séverine Monnerat Cristina I Almeida Costa Andrea C Forkert Corinna Benz Alana Hamilton Laurence Tetley Richard Burchmore Carlos Novo Jeremy C Mottram Tansy C Hammarton Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei. PLoS ONE |
| title | Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei. |
| title_full | Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei. |
| title_fullStr | Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei. |
| title_full_unstemmed | Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei. |
| title_short | Identification and Functional Characterisation of CRK12:CYC9, a Novel Cyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei. |
| title_sort | identification and functional characterisation of crk12 cyc9 a novel cyclin dependent kinase cdk cyclin complex in trypanosoma brucei |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0067327&type=printable |
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